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juniperpublishersanesthesia · 5 years ago

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Thromboelastography and Thromboelastometry in Patients with Sepsis - A Mini-Review-Juniper Publishers

Introduction

Coagulopathy is a common finding in patients with sepsis and is considered to be a risk factor for mortality [1]. Mechanisms like imbalance between coagulation and fibrinolysis have been attributed to coagulopathy in sepsis. The spectrum of coagulopathy can range from a hypercoagulable state to a hypocoagulable state [2]. Conventional coagulation assays (CCAs) like prothrombin time (PT) and activated partial thromboplastin time (aPTT) are routinely done to assess coagulation status in patients with sepsis. However, these coagulation tests have certain inherent limitations associated with them [3]. These limitations include their inability to detect hypercoagulable state and also cannot assess the fibrinolytic system. Rotational thromboelastography (TEG) and thromboelastometry (ROTEM) evaluate whole clot formation and can be useful point-of-care tests [3]. There is ongoing research to establish the efficacy of TEG/ROTEM over conventional coagulation tests in detection of hypo- or hypercoagulable states in sepsis and in guiding transfusion practices [4].

Basic principles of conventional thromboelastography (TEG®) and thromboelastometry (ROTEM®): [3,4]. The basic principle of functioning is similar in both thromboelastography (TEG®) and thromboelastometry (ROTEM®) with only subtle differences. Rotational thromboelastograph (TEG®) analyzer has a pin and an oscillating cup. However, in thromboelastometry (ROTEM®), the pin rotates and the cup remains fixed. Once blood begins to clot, fibrin strands are formed which influence the movement between the cup and the pin. This process is detected electromechanically and finally presented as a computerized tracing known as the thromboelastograph. Thromboelastograph is a waveform which depicts certain parameters that reflect different phases of the clotting process. These parameters are mentioned below:

An overview of TEG/ ROTEM with terminologies is presented below

A. Clot formation

Reaction time (R): R time represents the time of latency from start of test to the first evidence of clot or initial fibrin (or time taken for clot to achieve an amplitude of 2 mm) and it correlates with the level of clotting factors. In ROTEM®, R time is represented by clotting time (CT).

B. Clot kinetics

K time: K time is a measure of clot strength and it reflects the time taken for clot to reach an amplitude of 20 mm from the start of clot formation. It is recorded from the end of R time. In ROTEM®, K time is represented by clot formation time (CFT).

α angle: α angle is the angle along horizontal axis of thromboelastograph and it measures the speed at which fibrin build up and cross linking takes place. Hence, it assesses the rate of clot formation. a angle is the common terminology for this angle in both conventional thromboelastography (TEG®) and thromboelastometry (ROTEM®).

Either K time (or CFT) and a angle correlate with fibrinogen levels

i. Clot strength

Maximum amplitude (MA): MA measures the ultimate strength of fibrin clot and correlates with the level of platelets. In ROTEM ®, MA is represented by maximum clot firmness (MCF).

ii. Coagulation index (CI)

CI is calculated by a complex mathematical formula calculated from R, K, α and MA and has a normal reference range between -3 to 3. It is an overall indicator of coagulation and represents hypocoagulable (CI<-3), normocoagulable (CI -3 to 3) or hypercoagulable states (CI >3).

iii. Clot lysis (Fibrinolysis)

A30: A30 is the amplitude at 30 minutes post-MA (in both conventional thromboelastography and thromboelastometry).

Lysis index (CL 30%): CL 30 indicates the percentage decrease in amplitude 30 minutes post-MA. LY 30% represents the lysis index in thromboelastometry.

Estimated platelet lysis (EPL %): EPL is the computer prediction of diminution of amplitude 30 seconds post-MA and it is the earliest indicator of abnormal clot lysis (in bothconventional thromboelastography and thromboelastometry).

Hypocoagulability is defined as increased CT/R and CFT/K times and/or decreased MCF/MA and alpha angle.

Hypercoagulability is defined as decreased reaction times (CT/R and CFT/K times) and increased clot formation (increased alpha angle or high maximal amplitude (MCF/MA).

The thromboelastograph parameters are also useful in the diagnosis and management of hypocoagulability and hypercoagulability, identification of primary and secondary hyperfibrinolysis and differentiating between medical and surgical causes of bleeding (Table 1).

Studies on the ability of ROTEM® and TEG® to detect sepsis-induced coagulopathy or disseminated intravascular coagulation (DIC)

Results of TEG®/ROTEM® in sepsis have varied widely across the studies. Some patients have shown distinct hypocoagulabilty while others have shown a predominant hypercoagulable pattern. There are several reasons to explain this lack of uniformity in test results. The timing of measurement has varied widely in the studies. The initial phase of sepsis is characterized by formation of microvascular thrombi and the later phase manifests as a hypocoagulant phase secondary to consumptive caogulopathy. So, the timing of measurement has a bearing on test results. This heterogeneity can also be explained by the difference in disease severity of study population. Interestingly, there is no universally validated reference value and definition of hypocoagulability and hypercoagulability of ROTEM®/TEG® in the available studies. Overall, if sepsis- induced coagulopathy was present, ROTEM®/TEG® could detect it in 43-100% patients.

Some of these studies are mentioned below

Collins and co-workers investigated 38 patients with severe sepsis by performing global tests of haemostasis and compared them with 32 controls. They found that although patients with severe sepsis had a delayed activation of haemostasis but once initiated, thrombin generation and clot formation were normal or even enhanced in this group. Routine coagulation assays, which measure only the initiation of clotting process and not its propagation, poorly evaluate the coagulation capacity of such patients [8].

Role of ROTEM® and TEG® for anticoagulant treatment in sepsis

There are only few studies attending to this area with very small series of patients [11].

Role of ROTEM® and TEG® in prediction of outcome in sepsis

Hypocoagulability has been found to be an independent predector of poor outcome in some studies as mentioned below:

Daudel and co-workers in 2009 studied 30 patients with sepsis. Routine clotting tests and thromboelastometry (ROTEM®) were done every 12 hrs during first 48 hrs of admission, and finally at discharge from ICU. It was observed that patients with more severe organ failure (SOFA>10) had higher CFT (125±76 sec vs 69±27 sec) and lower MCF (57±11 mm vs 69±27 mm) as compared to those with less severe organ failure (SOFA<10). The values changed significantly with the intensity of sepsis. Improved organ dysfunction upon discharge from ICU was associated with shortened coagulation time, accelerated clot formation and increased firmness of blood clot [12].

Adamzik and co-workers in 2011 performed a study in 98 patients with severe sepsis to investigate the role of thromboelastometry (ROTEM®) as a potential predictor of 30-day survival in severe sepsis and compared ROTEM® with simplified acute physiology II (SAPS II) and SOFA scores. CT, CFT, a angle, MCF and SAPS II and SOFA scores were recorded on the day of diagnosis of sepsis. Mean CFT was significantly prolonged (276 ± 194 sec vs. 194 ± 109 sec) and both MCF (52.7 ± 12.1 mm vs. 57.3 ± 11.5 mm) and a angle (53.4 ± 12.8 degrees vs. 58.9 ± 11.8 degrees, P = 0.028) were significantly reduced in non-survivors. SAPS II and SOFA scores were not different between survivors and non-survivors [13].

Ostrowsky and co-workers in 2013 studied 50 patients with severe sepsis. Patients were divided into 3 groups on the basis of MA value of TEG® on admission: hypocoagulable MA, normocoagulable MA or hypercoagulable MA. Patients progressing to hypocoagulability had higher SOFA and DIC scores and they also showed a higher early mortality [14].

Conclusion

In summary, both thomboelastography (TEG®) and thromboelastometry (ROTEM®) seem to have a promising role in the evaluation of coagulation abnormalities in sepsis. But the available studies in sepsis show heterogeneous results and are of limited quality [4].

TEG/ROTEM measurements in sepsis can show both hypo- and hypercoagulability. Hypercoagulability is seen more in acute phase of sepsis. Timing can influence the results because sepsis is a dynamic process. Sequential measurements of TEG/ ROTEM can enlighten us more about coagulation derangements associated with sepsis. The current evidence is limited due to heterogeneity, small sample size, lack of standardized definitions for hypo- and hypercoagulable states. Larger trials can establish the utility of TEG/ROTEM to detect coagulation abnormalities to diagnose DIC and to guide transfusion therapy.

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juniperpublishersanesthesia · 5 years ago

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Negative Inspiratory Pressure as a Predictor of Weaning Mechanical Ventilation-Juniper Publishers

Introduction

Mechanical ventilation (MV) is a widely used resource within intensive care units (ICUs) for the maintenance of the lives of critically ill patients. However, its prolongation is associated with several complications, such as pneumonia, hemodynamic disorders, lung injury and diaphragmatic dysfunction; the latter defined as the set of structural and functional alterations produced by the inactivity of the diaphragm muscle during MV [1,2].

Several investigations developed since the 1990s on the impact of MV have been able to show changes in the diaphragm as a consequence of the prolonged use of positive pressure in the airway [2-5]. These changes reduce and modify the correct diaphragmatic functioning, making the weaning process more complicated and delayed due to the difficulty for the patient to spontaneously assume ventilatory work [2,3]. This translates into an increase in the number of hospital stay days, and consequently, costs in health services [6,7].

For all of the above, early ventilatory weaning is established as one of the main objectives in the management of the critical patient and its initiation should be considered from the moment the cause of the use of ventilatory support improves [8]. The success of weaning is defined as the maintenance of spontaneous breathing for at least 48 hours after discontinuation of MV. If the need to return to artificial ventilation arises during this period, it may be thought that weaning has failed [9]. It is considered that approximately 55% of the patients manage to pass this process without difficulties [10]; However, between 20 and 30% of the patients who are weaned from the ventilator present respiratory complications after extubation, requiring the reinstatement of the artificial airway [11].

Weaning failure can be due to several factors, summarized in four groups: alterations in gas exchange, hemodynamic instability, respiratory pump failure and psychological dependence on the ventilator [12]. This fact occurs in many cases because weaning is based on clinical judgments and individualized styles, behaviors that favor the prolongation of MV time [13]. Herein lies the importance of establishing a protocol of weaning and extubation systematically, integrally and preferably universal within the ICUs.

However, most of these criteria are not always statistically reliable because they present low sensitivity and specificity, and may give rise to the appearance of false positives and false negatives. In summary, precise parameters included within the weaning protocol do not always exist to predict the success or failure of weaning and extubation [11].

One of the predictors that has been contemplated in recent years to estimate the success of weaning is the maximum inspiratory pressure, commonly known as PIM, defined as maximum pressure that can be generated against an occluded airway for 20 seconds from the capacity Functional residual; In this sense, can be considered as a direct marker of inspiratory muscle function, and in particular, of diaphragmatic force [14].

The first time we talked about IMP measurement in critically ventilated patients was in 1973, when Sahn and Cols.la included within the extubation criteria, along with the value of minute ventilation and maximum voluntary ventilation. The research concluded that patients with values >30cm H20 are able to maintain their mechanical ventilation spontaneously [15]. On the other hand, in 1975 Feeley et al. [16] reported that the inspiratory force should be ≥20cm H20 to interrupt assisted ventilation.

In 1993, Strickland and Hasson developed an automatic weaning stool system for postoperative patients. Within the inclusion criteria to begin weaning, they added the Negative Inspiratory Force (NIF) denomination that until then had not been handled to refer to maximal inspiratory pressure [17].

Yang and Tobin performed a prospective study where they established the predictive indexes of the results of ventilatory weaning, taking NIF as one of them. In their research, they determined that inspiratory pressure is a better predictor of failure than of weaning success [18]. In contrast, Ebeid and Cols. Deduced in 2013 that NIF is a good predictor of weaning success [19].

It has been established that a NIF ≥-20 or -25cm H2O is adequate to initiate ventilatory weaning; With a NIF>-30cm H2O, there is a 93% chance of successful weaning [20,21], and on the contrary, with a NIF of >-15 or >-10cm H2O, patients are unable to breathe on their own (twenty-one). Parallel to this, values of -33cm H20 with a 50% mortality decrease -28cm H20 with 42% and -26cm H20 with 32% respectively have been associated [22].

Recently, we conducted a study with Colombian population, considering the measurement of NIF as a parameter of evaluation of diaphragmatic dysfunction in MV, which is being submitted for publication, considering that its use in patients submitted to MV is possible thanks to its Incorporation into state-of-the- art mechanical fans. The measurement is done by an invasive technique, simple and well tolerated by the patients. Thus, the value of NIF is presented as an effective alternative to take into consideration, both to assess the degree of diaphragmatic injury, to initiate weaning and to perform extubation.

Although NIF seems to be the most adequate measure to quantify the degree of pulmonary dysfunction in patients with ventilatory support, depending on the probability of success or failure of weaning, the information that can be found on its application within critical care remains limited and discordant, Which makes it necessary to carry out more research in which NIF is considered as a parameter of evaluation for respiratory dysfunction within a structured battery or as a potential extubation criterion.

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juniperpublishersanesthesia · 5 years ago

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Safest Anesthetic Technique for Hip Fractures in Elderly-Juniper Publishers

Background

There is high incidence of perioperative complications in hip surgeries after femoral neck fractures in older age group.

Objective

In this review, we try to detect the safest anesthetic technique for those patients.

Introduction

Hip fracture is a worldwide problem affecting 1.6million and will affect 2.6 annually by 2025 [1].Hip fractures are associated with high risk of morbidity and mortality, approximately 1-6% of patients will die during their hospital stay [2-4], 4-10% will die with in 30 days of their admission [5], and 18%- 28% of the patients die with in one year of their fractures [6] this is mainly due to pulmonary and cardiovascular complications [7]. Postoperative delirium is a frequent complication in elderly patients with hip fractures and the incidence is varying between 16% and 62% [8]. Patients with femoral neck fracture can experience delirium three times more than patients undergoing non orthopedic surgery [9]. Postoperative delirium is associated with high morbidity and mortality and prolonged hospitalization with subsequent increased suffering and cost [10]. There are many risk factors associated with postoperative morbidity and mortality in such age group of patients. Adequate preoperative treatment of respiratory problems (COPD, asthma) and prevention of postoperative cardiovascular complications (hypotension, hypertension, arrhythmia, ischemia, heart failure) may be the most important factor in reducing postoperative mortality after hip fracture surgery [11]. Cardiovascular, respiratory and neurological complications are well correlated to age, preoperative bedridden state, neurological comorbidities, preoperative delirium, and frequent intraoperative hypotension.

Anesthesia type

The influence of anesthesia type on mortality and morbidity in hip fracture surgery is certainly a controversial issue in the literature. Regional anesthesia has significantly reduced incidences of deep venous thrombosis, surgical site infection, pulmonary complications, and amount of blood loss. General anesthesia has a lower incidence of hypotension and cerebrovascular accidents [12]. A retrospective cohort study based on a nation wide sample of hospital admissions found that, there was no significant difference in risk of mortality with type of anesthesia in patients undergoing hip fracture surgery [13]. Regarding thirty days mortality another study found that, spinal anesthesia was associated with significantly lower incidence of thirty days complications than general anesthesia in hip fracture surgery [14]. Liu et al. [15] found that there was no significant difference in post-operative mortality and complications between general anesthesia and peripheral nerve blocks in these cases [15]. Jin et al. [16] found that there was no significant difference between peripheral nerve blocks and epidural anesthesia in hip fracture surgery regarding postoperative mortality and complications [16]. Continuous spinal anesthesia and ultrasound guided combined psoas compartment-sciatic nerve block (PCSNB) produced satisfactory quality of anesthesia in elderly high risk patients of hip replacement surgery but hemodynamic changes were fewer in us guided PCSNB [17].

Conclusion

A variety of appropriate anesthetic techniques can be used according to the patient individual condition regarding patient choice, comorbidities, psychological make up, anesthetist previous experience, surgical procedure, hospital facilities including funds available and postoperative care.

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juniperpublishersanesthesia · 5 years ago

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Understanding the Three Principal Goals of Clinical Airway Management-Juniper Publishers

Introduction

There are three main goals of clinical airway management-appropriate oxygenation, appropriate ventilation, and protection of the airway from injury. Let's briefly look at each of these goals.

Oxygenation

Oxygenation is controlled via the concentration of oxygen (fraction of inspired oxygen - Fi02) delivered to the patient, although "PEEP" adjustment can be equally important to improve oxygenation in ventilated patients with acute lung injury (PEEP or positive end expiratory pressure, is the minimum lung distending pressure over expiration during positive pressure ventilation; it is usually set between 2 and 5 cm H2O in patients with normal lungs). The minimum oxygen concentration used during general anesthesia is usually 0.3 (30%) and can be increased to 1.0 (100%) by decreasing the concentration air administered (or of nitrous oxide (N2O) in patients where this is used during general anesthesia). As a rough rule one adjusts FI02 (and PEEP in specialized settings) to keep arterial oxygen saturation above 94% (using a pulse oximeter) or keeping the arterial oxygen tension (PaO2) between 100 and 150 mm Hg in patients where arterial lines are available for arterial blood gas analysis.

Ventilation

In spontaneous ventilation (negative pressure ventilation), negative pressure inside the lungs from diaphragmatic flattening draws in air. It is important that clinicians recognize when a patient is not adequately ventilating; reasons could include inadequate respiratory effort (e.g., from excessive opioids, partial or complete airway obstruction (e.g., from airway edema) or both. If the patient is not breathing adequately one generally starts with a simple maneuver such as a chin lift or jaw thrust to help open the airway, with positive pressure ventilation with a bag-mask device being the next step if this intervention proves to be ineffective. Concurrently, in cases of suspected airway obstruction, the clinician physician must take measures to alleviate the obstruction. Prolapse of the tongue into the posterior pharynx due to loss of tone in the submandibular muscles is a frequent cause in unconscious patients. While a chin lift or jaw thrust is often sufficient adequate chest ventilation, some cases require that an artificial airway be placed (discussed later). Also, if one hears "gurgling" with breathing the oropharynx should be suctioned.

With positive pressure ventilation (PPV) gas is forced into the lungs using a positive pressure source such as a manual resuscitator or an automatic ventilator. PPV is often facilitated with muscle relaxation ("paralytics") but it is not generally necessary. With conventional ventilators, ventilation is determined by adjusting two parameters: tidal volume (TV) and respiratory rate (RR). To ventilate a typical patient using a ventilator, start with TV=7- 10ml/kg and RR=10/min and then adjust according to obtained end-tidal CO2 levels (ETCO2) (obtained via capnography) or from arterial carbon dioxide tension (PaCO2) measurements. On some older anesthesia machines the tidal volume delivered depends on the total fresh gas flow (FGF), often set between 1 and 6 liters/min (flows of 1-2 liters/min are most economical).

Protection of the Airway from Injury

A final important goal of clinical airway management is preventing lung injury that may result from various causes such as [1] gastric contents spilling into the lungs (aspiration pneumonitis) [1], [2] retention of secretions that may lead to pneumonia, or [3] partial lung collapse (atelectasis). The prevention of aspiration in unconscious patients (generally those under general anesthesia or patients with a head injury) is usually achieved by using a cuffed endotracheal tube; unintubated patients may develop deadly aspiration pneumonitis and ARDS (adult respiratory distress syndrome) [2] if stomach contents spill into the lungs (especially if the pH is <2.5 or volume >25ml). Patients at risk of aspiration with the induction of general anesthesia are usually managed with either a rapid sequence induction (RSI) or with awake intubation.

Finally, note that lung ventilation itself can sometimes be the cause of lung injury ("ventilator-associated lung injury") [3,4]. Numerous studies have proven that imprudent lung ventilation can cause inflammatory damage to the lungs from repetitive closing and reopening of the alveoli, barotrauma (trauma from excessive pressure), and volutrauma (trauma from excessive lung expansion). Even worse, induced systemic inflammatory changes from imprudent ventilation may even cause dysfunction or failure in other organs.

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juniperpublisherspediatrics · 5 years ago

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The Promotion of Adult’s Health from Childhood. Practical Training-Juniper Publishers

Perspective

The practical training to the students of school teacher is designed to serve to rein force the contents of the theoreticallessonsemphasizing the importance of respecting the timing of child’sgeneral and languageinterests. We consider necessary this clarification as our intervention in the training future. Teachers is limited to those who are going to teach children before six years old (infant school). The primary and secondary schooling remains outside, for the moment, in our scope.

Its content is focused mainly for the child to acquire practical skills and strengthen their interests and attitudes in the problems of health and its prevention in the own childhood and adulthood. Some important aspects for the prevention of the diseases of civilization that have been included in the theoreticaltalks are beyondpracticalconsideration because its inclusion would be out of context. We refer to such important issues as the toxic habits (smoking, alcohol, consumption of illegaldrugs, etc.,). Weemphasize the content more directly related to healthy nutrition, physical exercise, and the personal hygiene of the child. The practical aspects of the subject include two kinds of activities according to the permanence of the teacher during its development [1-7].

Practical Classroom Teaching. It is Composed of Three Types of Activities

Activities upon completion of the theoretical exposition of each lesson. They are intended to strengthen the contents explained by examples of common knowledge as well as the teacher can take advantage of immediate reality. During the last halfhour of the class are exposed topics-related activities. For example, students are asked that they value on the issue of school canteens, a school menu for children of a certain age, calculating calories provided by composition tables of foods, caloric distribution, and by using different food according to the Food Pyramid. For the realization of these works, they must attend web resources listed to the students.

Practices of basic cardio pulmonary resuscitation (CPR). Its purposeis to train future teachers in the application of first aid in case of accidents and urgent severe episodes. Workshops of CPR last two hours where students must complete basic activities of PCR using puppets. Professor trains students on value pulses, effort and respiratory rate and cardiac massage.

Seminars and workshops during the weeks of follow-up. Throughout the four months period of the course there are two free weeks from regular education. These general gaps of the teaching periods facilitates the revision of the whole matter given up to the moment as well as the articulation with other related materials. Held seminars on nutritional topics. The workshops aim to that future teachers are acquainted with practical issues that later must teach their students. For example, a workshop reviews the information provided by the food containers and assess whether this is correct. Students will go to super markets to examine the exposed foods.

Non presential practical teaching

a. Work Groups:They are activities aimed to promoting the personal initiative andwork as a team. They are the mostcontroversial issues as didactic tasks could providemany diverse developments. Students are distributed into groups of ten, and a project of the matter is assigned to each of them. The work may consist of the elaboration of a set of elements that integrate contents and teaching methodology of any child’s play or the preparation of explanatory posters on any aspect of the issue. Studentsmaterials must holdboth drawings and texts.

Limitations

The teaching of this subject faces several difficulties. In particular, the fact that this subject is taught during the first academic year, when students’ educational level is still rather limited, restrains students from thoroughly understanding the crucial importance of improving health during childhood and the eventual consequences in adulthood

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juniperpublisherspediatrics · 5 years ago

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The Promotion of Adult’s Health from Childhood. Practical Training-Juniper Publishers

Perspective

Practical Classroom Teaching. It is Composed of Three Types of Activities

Non presential practical teaching

Limitations

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juniperpublishersanesthesia · 5 years ago

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Dynamic Parameters do not Predict Fluid Responsiveness in Ventilated Patients with Severe Sepsis or Septic Shock-Juniper Publishers

Abstract

The dynamic parameters, stroke volume variation (SVV) and pulse pressure variation (PPV), are used to guide fluid resuscitation in ventilated patients. We investigated whether SVV, PPV and pleth variability index (PVI), an automatic measurement of the plethysmographic waveform amplitude changes, can be used to predict fluid responsiveness in ventilated patients with severe sepsis or septic shock. We measured cardiac index, (CI, transpulmonary thermodilution PiCCO2) SVV, PPV, global end-diastolic index (GEDI), central venous (CVP), arterial blood pressure and PVI (Masimo Radical 7) before and after infusion of 500ml Gelofusine® over 30min in 31 deeply sedated ventilated patients (tidal volume 8ml/kg) with severe sepsis and septic shock. We obtained one full set of measurements in 30 patients. 10 patients increased CI by at least 15% ("responders”), 20 patients were "non-responders”. Baseline haemodynamic variables were not significantly different between both groups. The area under the receiver operating curves (mean, SE) were 0.68 (0.11) for SVV, 0.66 (0.12) for PPV, 0.59 (0.12) for PVI, 0.55 (0.12) for GEDI and 0.75 (0.09) for CVP We concluded that none of the investigated dynamic parameters could reliably predict fluid responsiveness in ventilated patients with severe sepsis and septic shock in our study.

Introduction

Shock in sepsis results from vasodilatation and a reduction of effective intravascular volume. Its treatment, among others, includes optimal fluid resuscitation. Both over and under resuscitation can worsen outcome in these patients [1]. Routine clinical examination and static indicators of cardiac preload such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), or left ventricular (LV) end diastolic area, are poor predictors of fluid responsiveness [1,2]. Recent studies have shown that respiratory variations in the dynamic indicators of LV stroke volume (SV), namely pulse pressure variation (PPV) and SV variation (SVV) are more reliable predictors of fluid responsiveness in ventilated septic patients [3-5]. Respiratory changes in the amplitude of the plethysmographic pulse wave (ΔPOP) have been shown to be as accurate as PPV in predicting fluid responsiveness in ventilated septic patients [5]. Pleth variability index (PVI), an automatic and continuous monitor of ΔPOP, has been demonstrated to predict fluid responsiveness in ventilated patients undergoing general anaesthesia [6], and in critically ill ventilated patients with circulatory insufficiency [4]. However, it is unclear whether PVI specifically predicts fluid responsiveness in ventilated patients with severe sepsis or septic shock. Therefore, we conducted a prospective, non-randomised, nonblinded observational study to compare the ability of multiple dynamic and static cardiovascular parameters to predict fluid responsiveness in mechanically ventilated patients with severe sepsis or septic shock.

Materials and Methods

The study protocol for this observational study was approved by both national and local ethics committees and was conducted in accordance with the Declaration of Helsinki of the World Medical Association. A valid informed and written consent was obtained from patients' next of kin, after detailed explanation of the protocol, prior to enrolment into the study. Retrospective consent was obtained from all patients who survived to discharge from intensive care and regained mental capacity.

Patients

Thirty-one adult non-pregnant patients who required sedation and controlled mechanical ventilation for treatment of severe sepsis or septic shock, as defined by the International Sepsis Definitions Conference [7], were enrolled in the study. Patients were subjected to a fluid challenge (500ml of Gelofusine® administered over 30min) if they showed at least one sign of inadequate tissue perfusion (systolic blood pressure less than 90mmHg, urine output less than 0.5mlkg- 1h-1 for more than 2 hours, tachycardia greater than 100 beats per minute or capillary refill greater than 2 seconds). Patients were sedated with a continuous infusion of Protocol and Alfentanil. Infusions were titrated to achieve a Richmond Agitation Sedation Scale of -3. Patients were ventilated with a pressure controlled mode (BIPAP mode, EVITA 4 XL, Draeger, Germany) with a tidal volume of 8ml/kg estimated ideal body weight and a positive end-expiratory pressure of not more than 15cm H20. Respiratory rate was adjusted to achieve an arterial partial pressure of CO2 of 4.8-6kPa. The FiO2 was titrated to achieve an arterial saturation of >92%, the ratio of inspiratory versus expiratory time did not exceed 1:1. Exclusion criteria included any spontaneous breathing activity, a known allergy to Gelofusine®, any cardiac rhythm other than sinus rhythm, contraindications for a fluid challenge (PaO2/FiO2 less than 13.3kPa, pulmonary oedema on chest X-ray), patients unable to lie supine or peripheral vasoconstriction causing obliteration of the plethysmographic signal.

Haemodynamic monitoring

Invasive haemodynamic monitoring was performed by using either a 20cm 5-Fr thermistor-tipped arterial thermodilution catheter (Pulsiocath, Pulsion Medical Systems AG, Germany) inserted into a femoral artery or by using a 22cm 4-Fr thermistor-tipped arterial thermodilution catheter (Pulsiocath, Pulsion Medical Systems AG, Germany) inserted into a brachial artery. The tip of a central venous catheter (Arrow International Inc., Reading, PA, USA) was positioned in the superior cava vein confirmed by X-ray examination. Central venous blood gas samples were taken pre and post fluid challenge (ABL 725, Radiometer, Copenhagen, Denmark). The arterial catheter was connected to an advanced haemodynamic monitor (PiCCO2®, Pulsion Medical Systems AG, Munich, Germany). Thermodilution was performed using at least three cold fluid boluses randomly throughout the respiratory cycle and was repeated within five minutes prior to and five minutes post fluid administration. The patient was positioned supine for all measurements. Electrocardiogram, arterial blood pressure, CVP and arterial oxygen saturation (SaO2) were continuously monitored (Spectrum Monitor, Datascope Corporation, Montvale, NJ, USA) and all recordings were taken at end-expiration. A pulse oximeter probe (LNCS® Adtx, Masimo Corp., USA) was attached to the index finger of the right hand and wrapped to prevent outside light from interfering with the signal. This pulse oximeter probe was connected to the Masimo Radical 7 monitor (Masimo SET, Masimo Corp., Irvine, CA, USA) displaying perfusion index and Pleth Variability Index (PVI).

Conduct of the study

After ensuring at least a 5-minute period of haemodynamic stability, the first set of measurements was obtained. This was followed by a fluid bolus of 500ml Gelofusine® infused intravenously over 30min. The second set of measurements was obtained 5min after the fluid infusion was completed. Ventilator settings and dosages of inotropic, vasoactive and anaesthetic drugs were held constant throughout the measurements. At each step of the protocol, the following variables were recorded: Heart rate (HR), systolic, diastolic and mean arterial pressure (MAP), CVP, central venous oxygen saturation (ScvO2), SV, SV index (SVI), CO, cardiac index (CI), global end-diastolic index (GEDI), SpO2, PPV, SVV and PVI. All patients were kept in a supine position during the entire period of the study. Only one full set of data was obtained and analysed per patient.

Statistics

In accordance with previous studies [8], we took the criteria of a 15% increase in CI in response to the fluid challenge to differentiate responders from non-responders to fluid. The normality of distribution of data was tested using the Kolmogorov-Smirnov test. Parametric data are presented as mean with standard deviation or standard error and non- parametric data as median with inter-quartile range (IQR).

We compared non-parametric haemodynamic data before and after volume expansion in responder and non-responder patients using the Mann-Whitney U test. Wilcoxon signed rank tests were used to compare the response to fluid in responders and non-responders, respectively. Receiver operating characteristic (ROC) curves comparing the ability of CVP, SVV, PPV, GEDI and PVI at baseline to discriminate between responders and non-responders to volume expansion were generated varying the discriminating threshold of each parameter. Using the results from previously published studies [3], we conducted a priori power calculation which showed that 31 patients were necessary to detect differences of 0.1 between areas under the ROC curves with a 5% two-sided type I error and 80% power. A p-value less that 0.05 was considered as significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 20.0.

Results

Thirty-one patients were recruited. One patient declined to provide consent retrospectively. Complete sets of data were analysed for the remaining 30 patients. Baseline characteristics, as well as respiratory variables and vasopressor/inotropic requirements were not statistically different between responders and non-responders (Table 1). Ten patients increased CI by 15% or more after volume expansion and were classified as responders. 20 patients were classified as nonresponders. There was no statistically significant difference in any haemodynamic variable at baseline between the two groups (Table 2). Both responders and non-responders increased CVP and decreased PPV in response to the fluid challenge (Table 3 & 4). Only responders showed a statistically significant increase in GEDI (Table 3). Receiver operating characteristic curves (ROC) comparing the ability of CVP, SVV, PPV, PVI and GEDI to predict fluid responsiveness is shown in (Figure 1). The area under the receiver operating curves (mean, SE) were 0.68 (0.11) for SVV, 0.66 (0.12) for PPV, 0.59 (0.12) for PVI, 0.55 (0.12) for GEDI and 0.75 (0.09) for CVP (Table 5, Figure 1).

BSA: Body Surface Area; FiO2- Fraction of Inspired Oxygen; PEEP Peak End Expiratory Pressure; PaO2 Partial Pressure of Arterial Oxygen; PaO-2/ FiO2 Ratio of Partial Pressure of Arterial Oxygen with Fraction of Inspired Oxygen. Vasopressin and Adrenaline was used only in one patient each.

HR: Heart Rate; MAP: Mean Arterial Pressure; CVP: Central Venous Pressure; SVRI: Systemic Vascular Resistance Index; GEDI: Global End Diastolic Index; CI: Cardiac Index; PPV: Pulse Pressure Variation; SVV: Stroke Volume Variation; PVI: Pleth Variability Index; ScvO2, central venous oxygen saturation.

AUC: Area Under the Curve; SE: Standard Error; CI: Confidence Interval; CVP: Central Venous Pressure; SVV: Stroke Volume Variation; PPV: Pulse Pressure Variation; PVI: Pleth Variability Index; GEDI: Global End Diastolic Index.

Discussion

This study aimed to compare the ability of PVI with the more established parameters PPV, SVV, and GEDI to predict fluid responsiveness in mechanically ventilated patients with severe sepsis or septic shock. The main finding is that none of the above haemodynamic parameters were able to reliably predict fluid responsiveness despite exclusion of common known confounding factors. We observed a significant number of false positive and false negative results considering previously cited cut-off values for dynamic parameters in general ICU and more specifically in ventilated septic patients [4,5,8-10]. Our study population consisted of ventilated patients with severe sepsis and septic shock. All but three patients were receiving vasopressor support. Known confounding variables affecting the ability of dynamic parameters to predict fluid responsiveness were excluded: all patients were in sinus rhythm during the study period and did not have any arrhythmia; all were deeply sedated without any spontaneous breathing activity and received a tidal volume of 8ml/kg estimated lean body weight. Haemodynamic measurements were performed using the PiCCO 2 monitor which is a well validated accurate monitor measuring SV even in rapidly changing circulatory conditions [11] and in patients with reduced cardiac function [9]. At least three cold boluses were given randomly throughout the respiratory cycle using the same sampling period (30 seconds) to obtain relevant haemodynamic data using transpulmonary thermodilution [12]. In line with other studies, we used a fluid bolus of 500ml Gelofusine® administered over 30min [5]. The mean CVP increased after volume expansion in both responders and non-responders by at least 2mmHg (Table 3 & 4), which has been defined previously as a proof for an adequate fluid challenge [13]. We explored the possible reasons for the unexpected finding that none of the dynamic parameters reliably predicted fluid responsiveness in our study. Less than 50% of our patients were responders. This is not uncommon in critically ill patients with severe sepsis/septic shock or after cardiac surgery [10,14,15]. It is known that septic shock is frequently associated with biventricular dysfunction and increased pulmonary artery pressure [16]. Both RV and LV failure are well known confounders altering the magnitude and ability of PPV and SVV to predict fluid responsiveness [17]. Impaired RV function is also a frequent problem in ARDS, a condition commonly associated with septic shock [18]. In case of RV dysfunction/failure, one might observe "false" high PPV and SVV in non-responders as the RV after load, in contrast to preload change, is the major determinant for high PPV and SVV [14,19]. This could be further exacerbated by increased pulmonary artery pressure, large tidal volumes and high PEEP [18,20], the latter two of which were present in our study (Table 1). Previous studies on the ability of dynamic parameters to predict fluid responsiveness in septic patients either did not measure pulmonary artery pressure [5], pulmonary artery pressure was not significantly raised [3] or PEEP values were low [10]. In our study, all but three patients received vasopressors, which can independently increase pulmonary artery pressure. Daudel and colleagues demonstrated that, in contrast to haemorrhagic shock, in endotoxemic shock with raised pulmonary artery pressure, PPV did not predict fluid responsiveness [19]. A similar conclusion was reached by VanBallmoos who reported a reduced RV ejection fraction in almost half the non-responders and in none of the responders in patients with septic shock or post cardiac surgery [14].

In case of LV dysfunction/failure both PPV and SVV are generally decreased [3,17]. However, Mesquida et al have shown that if PPV and SVV are being used for fluid resuscitation in heart failure conditions, the phase relation between airway pressure and the maximal SV and hence PP needs to be determined [17]. If the LV is afterload dependent, one could observe a simultaneous increase in SV and hence PP when intrathoracic pressure increases and thus PPV and SVV might be high without reflecting fluid responsiveness particularly if the tidal volume is high and/or the chest wall is stiff e.g. due to sepsis induced oedema. For the haemodynamic measurements taken by the PiCCO system the phase relation between the change in airway pressure and maximal PP and SV is unknown. PPV and SVV are calculated over a 30sec rolling period. Reuter et al reported that SVV measured by the PiCCO system is still a reliable marker of fluid responsiveness in LVF with EF<35% [9]. However, in this study the AUC for SVV to predict fluid responsiveness in patients with impaired LV function was 0.76 which was lower than the AUC for SVV to predict fluid responsiveness in a second group of patients with normal LV function (0.88).

Gruenewald et al reported that in animals suffering from stunned myocardium shortly after cardiac arrest all dynamic parameters are unreliable in predicting fluid responsiveness [21]. Wiesenack and colleagues, found no correlation between SVV measured by the PiCCO system and prediction of fluid responsiveness in patients undergoing elective coronary artery bypass surgery, with an ejection fraction >50% [22]. In this study the authors speculated that arterial pulse contour- derived estimates of SVV are potentially unreliable under positive pressure ventilation. PPV is considered the more sensitive and specific parameter compared to SVV in predicting fluid responsiveness as pressure measurements are usually more accurate than SV measurements. However, in our study neither baseline SVV nor PPV could reliable predict fluid responsiveness. SV and PP are tightly correlated during positive pressure ventilation [17]. The magnitude of PP for any given SV depends on central arterial compliance. Thus, a vasopressor induced reduction in central arterial compliance could lead to large changes in PP and hence PPV even for small changes in SV. The majority of the patients in our study were treated with vasopressors and it is tempting to speculate that this might be a further explanation why some patients were unresponsive to fluids despite high baseline PPV. Furthermore, it is conceivable that a more pronounced inspiratory increase in PP is due to an exaggerated dUp phenomenon in the presence of reduced LV function [8]. which might have contributed to an increase in PPV in non-responders.

As the cyclic changes in RV and LV pre- and after load are dependent on cyclic changes in intraalveolar, intrapleural and hence transpulmonary pressure any factor affecting one or a combination of these would have an impact on all dynamic parameters. Increasing tidal volume directly increases the magnitude for PPV and SVV for any given chest and lung compliance [17]. Intraabdominal pressure affects chest wall compliance and hence intrapleural pressure. In fact, Jacques et al showed that the cut-off values for all dynamic parameters increase significantly if intraabdominal pressure is increased [23]. We did not measure intra abdominal or intrapleural pressure in our study. Respiratory system compliance was not significantly different in both groups. However, we cannot exclude the possibility that differences in transpulmonary pressures induced by the same tidal volumes might have contributed to our findings. Loupec et al showed that PVI reliably predicts fluid responsiveness in critically ill ventilated patients [4]. However, this result has not always been replicated in septic patients treated with vasopressors [10,15,24]. One possible explanation for this finding could be that the proportion of septic shock patients was lower in Loupec's study (55%) than in the other studies (85%, 86%) [4,10,15].

Conclusion

We conclude that the dynamic parameters PPV, SVV and PVI may not be able to predict fluid responsiveness in all ventilated patients with severe sepsis or septic shock even after exclusion of already commonly known confounding factors. An assessment of RV and LV function and measurement of intraabdominal or even transpulmonary pressure should be taken into account before interpreting and acting on the values measured. Passive leg raising, as a "reversible” fluid challenge might help to prevent unnecessary and potential harmful fluid loading provided intraabdominal pressure is not increased [25].

Acknowledgement

Hardware and software for the conduct of the study were supplied by Masimo Corp., Irvine, CA, USA.

The study was supported by a grant from the Research Development Department, The James Cook University Hospital, Middlesbrough, United Kingdom.

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juniperpublishersanesthesia · 5 years ago

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Supraorbital/Supratrochlear Nerve blocks: Clinical Significance of the Superior and Anterior Approaches-Juniper Publishers

Introduction

Hair restoration is one of the commonest cosmetic surgery procedure in men [1]. The procedure is performed under local anaesthesia. Many of the patients are anxious about the degree of pain to be expected during and after the surgery. The pain of the local anaesthetic agent is dependent on various factors like needle gauge, composition, temperature, pH, speed of injection, anatomical structure/area etc. Various maneuvers are used to decrease the pain during the administration of local anaesthesia like vibration anaesthesia Cryotherapy etc [2-4]. With the introduction of newer drugs for local anaesthesia, the safety is increased.

Peripheral nerve blocks constitute a major tool in the armamentarium in the office-based cosmetic surgery procedures. Supraorbital (SO) and supratrochlear (ST) nerve are the terminal branches of the frontal nerve [5]. These nerves supply mainly the skin of the forehead. These nerve blocks are beneficial in many procedures. The SO/ST nerve block during hair transplant surgery decreases the severity of the pain for recipient site injections. Their blockage is beneficial in treating disorders like trigeminal neuralgia, migraine etc [6,7]. These nerve blocks also result in significant decrease in the need of additional analgesics and opioids [8]. The SO/ST nerves collectively provide sensory innervation to the forehead and frontal scalp as well as to the vertex (Figure 1). The anatomical details and variations of these nerves is very essential for a proper anaesthesia.

The supraorbital (SO) nerve emerges from the supraorbital foramen or notch. The foramen or notch is located about 27 mm lateral to the glabellar midline. However, the distance varies if different races [9,10]. The nerve divides into medial and lateral branches. Similarly supratrochlear (ST) nerve emerges through supraorbital notch about 17mm from glabellar midline. It follows one of the four courses i.e., Ia (ST nerve emerges independently from SO nerve as a single nerve through Corrugator Supercilli muscle), Ib (ST emerges independently from SO nerve and bifurcates into 2 branches prior to entering the Corrugator Supercilli muscle), IIa (ST nerve emerges from SO notch with SO nerve and passes through Corrugator Supercillimuscle as a single nerve), and IIb (ST emerges from SO notch with SO nerve and bifurcates into 2 branches prior to entering the Corrugator Supercillimuscle) [11].

There are two techniques to accomplish SO/ST nerve block, i.e., anterior and superior. In superior approach, the needle is inserted from the cephalic side in such a way that the tip of the needle is felt at SO foramen by the palpating finger of the physician's other hand. Whereas in the anterior approach, the physician stands on the side of the patient and the needle is directed towards the midline. The following study was undertaken to compare the pain levels of anterior and superior approaches.

Materials and Methods

The study was conducted in 30 patients undergoing SO/ST nerve clock for hair restoration surgery. The patients undergoing 1st session were included. The informed consent was taken. All the injections were administered by the surgeon. A 3ml syringe with 30 oG needle was used containing 1% Xylocaine with adrenaline is 1;100,000 dilution. Separate needle was used for each side.

Superior Approach

The needle was introduced about 2cm above the SO foramen palpated. About 0.5ml of the anaesthetic solution was injected. The needle was advanced caudally till the tip was felt at the foramen and 0.5ml was injected here. The needle was withdrawn slightly and directed laterally injecting about 1.0ml in a 'fanning out' way. The needle was again withdrawn and directed medially injecting about 1.0ml. This technique encompassed all the possible branches of the SO/ST nerves (Figure 2).

Anterior Approach

The SO foramen was palpated and the needle was inserted from the front side of the patient. Care was taken not to puncture the SO nerve. About 1.0ml was injected here. The needle was withdrawn and 1.0ml was injected on medical and 1.0ml on lateral side (Figure 3). At the end of the procedure, the patients were asked to rate the pain according to the Wong Baker Faces Pain Scale [12] (Figure 4). The patients were also asked to give their feedback on the choice of technique for the next time. The data was analyzed statistically by Mann-Whitney's U-test (using the Easy Statistics Calculator©, version 1.2.0, Saitama, Japan, copyright 2016).

Results

A total of 35 patients were included in the study. The mean age was 33.4 years (range; 18 to 56). The mean pain score was 4.14 in anterior approach whereas 2.85 in superior approach (Table 1). About 31.4% of the patients were smokers. The pain score in smokers vs non-smokers was 4.09 vs 2.82 in anterior approach respectively. Where as in superior approach, the mean score was 4.27 vs 2.86 in smokers and non-smokers respectively. About 20% patients were anxious about the anterior approach that the needle may hit the eyeball. About 71.4% of the patients voted for superior approach on both sides for the next time.

Discussion

The role of SO/ST nerve block is well established in plastic surgery. It is routinely performed for the management of different kinds of headaches like tension headache, chronic headaches, migraine etc [6,7]. It is also the mainstay of regional anaesthesia in office-based cosmetic surgery procedures like hair restoration procedure [13]. To carry out a successful SO/ ST nerve block, the relevant anatomy is of utmost importance which helps to locate the nerves and block them.

The sensory innervation of the face is supplied by trigeminal nerve which has five branches4. The frontal nerve enters the orbit via superior orbital fissure and passes anteriorly beneath the periosteum of roof of the orbit. The frontal nerve gives off a larger lateral branch, the supraorbital nerve, and a smaller medial, supratrochlear nerve. The SO nerve exits the SO foramen or notch along the superior rim of orbit, accompanied by the artery and vein. In the notch or foramen, SO nerve gives off branches which supply mucosal membrane of frontal sinus and filaments which supply upper eyelid. Above the rim, SO nerve divides into superficial and deep branches.

The medical (superficial) branch passes over the frontalis muscle and divides into multiple smaller branches with cephalic distribution towards the hairline. It provides sensory innervation to the forehead skin and anterior scalp as far as the vertex. The deep branch (laterla0 runs deep in the frontalis across lateral forehead between galeaapo neuroticanad pericranium. It provides sensory innervation to underlying periosteum and frontal parietal scalp. The ST nerve is the branch of the frontal nerve and supplies sensory innervation to the bridge of the nose, medical part of upper eyelid and medial forehead. Usually ST nerve is located about 17mm from midline and SO nerve at 27 mm from midline.

The two approaches for SO/ST nerve block are well- established. The current study is first of its kind to compare the differences in terms of pain and patients' anxiety. The superior approach was found to be clinically/statistically significant (p<0.5). There are many factors which influence the experience of pain perceived by patient but the technique of SO/ST nerve block remained one of the significant factors. The visualization of watching the injection near the eyeball probably resulted in high level of anxiety in anterior approach.

The study by Chang et al described the pain of SO/ST nerve block to be between 1 and 2 (out of 10) whereas in the present study, the average pain score was 4.4 (out of 10) [14]. In another study, the average pain score was 3.9 (out of 10) and 6.8 9 out of 10) in SO/ST nerve block with and without the use of topical anaesthetic cream [15]. In another study, the mean score also remained 3.86 [16]. In these two studies, the anterior approach was used for administering SO/ST nerve block. In the present study, the pain score was found to be doubled in anterior approach as compared to the superior approach. The pain of superior approach remained 2.85.

Distraction during the administration of local anaesthesia injection plays a very important role [4,17]. In the present study, all the injections were administered by the surgeon. The needle gauge, room temperature and environment were kept the same in all the patients. The speed of the injection was kept slow and maintained by the surgeon to a very slow in all the patients. The Wong Baker Faces pain scale was used for rating as the scale gives the opportunity to the patients to express how they feel as it has a well established reliability and validity even in children [18,19].

Conclusion

The superior approach for administration of supraorbital/ supratrochlear nerve block proved to be better approach as far as the patient's anxiety about the injections is concerned. It also proved to be less painful.

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juniperpublisherspediatrics · 5 years ago

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Acute Steroid Induced Myopathy after Single IM Dose of Steroid-Juniper Publishers

Abstract

Introduction:AMS after a single IM dose of dexamethasone is very rare. And till now no one has reported similar case, on the other side the chronic myopathy induced by high IV corticosteroids is not unusual.

Case presentation:A 3 years old female had acute myopathy with rhabdomylosis after a single dose of steroid with rapid improvement after discontinued the medication

Conclusion:In spite of that our case is rare; the physician should pay attention while using steroids, especially when clinical situation and laboratory tests are highly suspicious.

Abbreviations:ALP: Alkaline Phosphatase; ALT: Alanine Aminotransferase; ASM: Acute Steroid Myopathy; AST: Aspartate Aminotransferase; CPK: Creatinine Phosphokinase; CRP: C-Reactive Protein; EMG: Electromyography; ESR: Erythrocyte Sedimentation Rate; IV: Intravenous

Introduction

Steroid myopathy is usually an insidious disease process that causes weakness mainly to the proximal muscles of the upper and lower limbs and to the neck flexors. Cushing originally described it in 1932, and Muller and Kugelberg first studied it systemically in 1959. An excess of either endogenous or exogenous corticosteroids is believed to cause the condition. Excess of either endogenous or exogenous corticosteroids is believed to cause the condition [1,2].

Corticosteroids were introduced into clinical practice in 1948, and in 1958, Dubois [3] reported the first patient with myopathy resulting from iatrogenic corticosteroids. Since corticosteroid therapy’s introduction into clinical practice, both acute and chronic steroid myopathies have been well recognized.

Chronic steroid myopathy is more common and develops after prolonged usage of steroids [3,4]. Acute steroid myopathy (ASM) is less common and develops early in the course of treatment, typically with high-dose intravenous (IV) steroids [4].

Earlier case reports of ASM usually involved patients with asthma receiving high-dose IV corticosteroids for status asthmaticus [5]. Geeta A Khwaja also reported on 2009 a case of Acute Myopathy Following Short-term Low-dose Oral Steroid Therapy in adult patient [6].

Acute myopathy developing from intramuscular corticosteroid has not been often reported. No case was found yet that described a pediatric patient developing myopathy after a single dose of intramuscular corticosteroid therapy.

Case presentation

A 3 years old, female known case of bronchial asthma step 1, was in usual healthy state till 3days back when she had upper tract infection which induced acute asthmatic exacerbation, this episode was treated by nebulized albuterol (ventolin) and one dose of IM dexamethasone (0.5 mg /kg /dose), respiratory symptoms improved but after 24 hours. The patient had generalized muscle weakness and myalgia with no skin rash or joint problem, after that her urine became dark.

Her mother sought medical advice in our ER, and she mentioned 2 similar attacks after steroid injections but without urine color changing.

On examination, the patient looked ill with stable vital signs, no skin rash

She was admitted for further investigation, where laboratory tests revealed

ESR=11 mm/h, high liver and muscle enzymes CK =3200 LDH=404 AST=242 ALT=41 ALP=109

Other serum biochemistry levels and renal function were normal

Urine dipstick showed 4+ blood, urine analysis confirmed presence if myoglobin.

Rhabdomyolysis was suspected and treated by adequate hydration and urine alkalizing.

The patient clinically improved and urine became clear

Rheumatologist excluded connective tissue disease, including dermatomyositis.

Depending on acute course and rapid recovery neurologists diagnosed this case as rhabdomyolysis resulting from acute steroid myopathy.

After 4 days of admission, she was discharged with follow up as an outpatient.

EMG was done as outpatient and was normal; unfortunately the nerve conduction study was not done.

The following Table 1 is showing muscle and liver enzymes during admission.

After 2 weeks: The patient was doing well with normal physical examination and LDH =200 CK=250 ALT=44 AST= 53

Discussion

Steroid myopathy may be more frequent with the use of fluorinated steroids, such as dexamethasone or triamcinolone, than with nonfluorinated ones, such as prednisone or hydrocortisone. [5, 6] Although the exact mechanism of the muscle pathology is unclear, it may be related to decreased protein synthesis, increased protein degradation, alterations in carbohydrate metabolism, mitochondrial alterations, electrolyte disturbances, and/or decreased sarcolemma excitability [1].

Most of studies have shown that myoglobinuria secondary to drugs, when considered in the pediatrics population, occur more so in the seconds decade of life, our case elluded to the fact that it can occur in younger age groups as well [7].

Hypokalemia can induce rhabdomyolysis but in our patient, hypokalemia, as secondary to perhaps B2 agonist, or corticosteroids, could not have contributed to the development of myoglobinuria, as the patient’s biochemistry profile was normal [8].

The acute form of steroid myopathy is uncommon. It usually occurs in ICU patients who receive high dose IV corticosteroids and/or nondepolarising neuromuscular blocking agents to facilitate mechanical ventilation, but can occur with high-dose glucocorticoid use alone [6].

Acute, generalized weakness, including weakness of the respiratory muscles, typically occurs 5-7 days after the onset of treatment with high-dose corticosteroids.

Generalized muscle weakness, not limited to a more proximal distribution is noted.

Muscle stretch reflexes typically are normal and sensory examination should be normal [1]. Though most cases in the literature report a lengthy prolonged recovery phase sometimes taking 3-12 months for full recovery, our patient exhibited a rapid recovery….. one such speed recovery was reported.

In acute steroid myopathy, most patients have high levels of serum creatine kinase (CK). AST, ALT, as well as associated myoglobinuria.

Our patient, however fortunately did not develop ARF, as the serum urea nitrogen and serum creatinine remained within normal limits. It is recommended that a low threshold of clinical suspicion be employed; and serum CK as well as urine dipstick and microscopy to detect myoglobinuria should be obtained for patients in whom rhabdomyolysis may be possible [9]

in adults is not diagnostically helpful EMG was normal in our case.

Interestingly, gender also seems to be a risk, as women are twice as likely as men to develop muscle weakness [10]… of note. Our patient was also a female, hence, there was a gender predilection for the likelihood of developing drug induced acute rhabdomyolysis.

Treatment of ASM is aiming to discontinue the rhabdomyolysis and prevent developing renal failure. No definitive treatment was found in literature except only to stop giving steroid, in addition to that weakness seen with steroid myopathy typically resolves after the corticosteroid dose is reduced or discontinued.

This case revealed clearly that even single IM dose of steroid can cause ASM.

Conclusion

We think that steroids still a cornerstone of treatment for most areas of Medicine, and it is unwise to abandon this drug, and despite the rarity of this case, our clinical threshold should be low to discover it, even after single dose.

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juniperpublisherspediatrics · 5 years ago

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Neonatal Lung Abscess-Juniper Publishers

Neonatal lung abscess

A baby girl was born at 23+4 weeks by precipitate delivery following spontaneous onset of labour and PROM of 121 hours. Mum had received a course of antenatal steroids. Following two unsuccessful trials of extubation on day 7 and 12, she had a significant cardio respiratory deterioration on day 14. She was started on second line antibiotics. Her CRP went up to 20 and her platelet count dropped to 51. Her chest x ray showed a large bullous emphysematous lesion occupying almost all of her right middle lobe (Figure 1 & 2). She became increasingly difficult to ventilate with worsening acidosis, hypotension and hyperglycemia despite maximizing intensive care support. Following discussion with her parents, her care was redirected to a palliative course. Post mortem examination of lungs revealed widespread collections of neutrophils / abscesses consistent with congenital pneumonia with abscess (seen as cavitating lesion on imaging). Her blood cultures did not reveal any growth.

Neonatal lung abscess is very rare [1] and is often of multibacterial etiology [2,3]. Predisposing factors include prematurity, assisted ventilation, congenital lung anomaly and aspiration. Given the range of potential pathogens, direct culture by percutaneous needle aspiration under either ultrasound [4] or CT guidance [2] is recommended to direct early appropriate intravenous medical therapy and hasten recovery, prevent further complications and obviate the need for surgery [4].

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juniperpublisherspediatrics · 5 years ago

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Neonatal Lung Abscess-Juniper Publishers

Neonatal lung abscess

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juniperpublishersanesthesia · 5 years ago

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Radiation-Induced Vasculopathy-Juniper Publishers

Introduction

A 54 year-old man had several months of near-syncope and global weakness occurring typically with walking that worsened after starting antihypertensive medications including a diuretic. He had been treated for Hodgkin's lymphoma, presenting as a nasal mass as a young adult, with chemotherapy and external beam radiation. He had a normal head CT and felt somewhat better after receiving intravenous fluids but his symptoms returned on ambulation. MRI and MRA (Figure 1) of his head and neck showed occlusion of his left common carotid artery, highgrade stenosis (>75%) of his right internal carotid artery, and severe disease of both vertebral arteries; MRI showed numerous scattered punctate infarctions We started a Heparin infusion, held all antihypertensive medications allowing for permissive hypertension, and consulted Vascular Surgery for urgent right carotid endarterectomy. His recovery was complicated by postoperative infection but he had no further neurological symptoms at his three month follow-up visit.

Radiation-induced vasculopathy may take years to decades to become clinically symptomatic. Diuretics and vasodilators may worsen cerebral perfusion and exacerbate symptoms potentially leading to stroke [1-5].

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juniperpublisherspediatrics · 5 years ago

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Pulmonary Hypertension in Children with Esophageal Varices: Frequency and Relation to N-Terminal Pro B-Type Naturetic Peptide-Juniper Publishers

Abstract

Classical homocystinuria (CHU) due to Cystathionine Beta-Synthase (CBS) deficiency is rare autosomal recessive inborn error of amino acids metabolism causing accumulation of methionine and homocysteine. The clinical manifestations of CHU may include neurological deficits mostly due to thromboembolic event so the most common brain radiological findings are secondary to stroke. The management is based on pharmacological treatment and dietary restriction of methionine. We present four patients with pyridoxine non-responsive CHU, who were found to have white matter changes on brain MRI, with a review of their clinical characteristics and neurological outcome. All patients had an underlying homozygous mutation of c.1006C>T (p.R336C) in the CBS gene, hypermethioninemia due to poor adherence to diet restriction, and were diagnosed before the implementation of the National Metabolic Newborn Screening Program in Qatar. Dramatic reductions in methionine levels because of better compliance were associated with reversibility of the brain white matter lesions in two patients.

Introduction

Classical homocystinuria (CHU) due to Cystathionine Beta-Synthase (CBS) deficiency (OMIM 236200) is a rare autosomal recessive in born error of amino acids metabolism [1]. Degradation of dietary methionine produces an intermediate compound known as homo cytosine that is mostly re-methylated to methionine. Homocysteine is also converted to cystathionine by the action of CBS which requires pyridoxine (Vitamin B6). Cystathionine Beta-Synthase deficiency due to CBS gene mutation leads to accumulation of both methionine and homocysteine, (Figure 1) [2]. The estimated prevalence of Classical homocystinuria is between 1/20,000 and 344,000. However, in Qatar it is approximately 1/1,800 births, the highest in the world [3-5]. Untreated patients may present with multisystem manifestations, such as vision problems due to myopia and ectopia lentis, osteoporosis, skeletal deformities mimicking Marfan syndrome, intellectual disability, and thromboembolic events. Neurological presentations may include seizures, extra pyramidal signs, psychiatric disturbance and focal neurological deficit due to infarction [5-7].

Neuro-imaging is not routinely done for patients with classical homocystinuria unless clinically indicated. The most common brain radiological findings are secondary to stroke: infarction, atrophy, and venous occlusion [7]. Classical homocystinuria is classified into pyridoxine responsive and none responsive types, homozygous mutation of c.1006C>T (p.R336C) in the CBS gene was attributed for most of pyridoxine non-responsive homocystinuria among Qatari patients [4].

Protein (Methionine) restricted diet and pharmacological treatment with pyridoxine (Vitamin B6), Betaine, hydroxy-cobalamine (Vitamin B12), and folic acid, are the corner stone in managing patients with classical homocystinuria. The aim is to control biochemical abnormalities and prevent complications.

Newborn screening is essential to improve clinical outcomes and patient’s quality of life by allowing early diagnosis and management. Poor compliance to diet restriction and medical treatment leads to hypermethioninemia and serious complications [8,9].

Case Series

Case 1

An 18 year old, male was diagnosed with classical homocystinuria by the age of 7 years. He was born at term after uncomplicated pregnancy and a smooth antenatal history. He was hospitalized at age of 5 months for acute bronchiolitis and at 10 months with intussusceptions that was reduced by barium enema.

At 7 years of age, he presented with history of limited vision and poor school performance. Physical examination showed, tall stature, slender body constitution with height falling at the 90th percentile and weight falling just below 50th centile, long face, long tibial bones, but no scoliosis or kyphosis. Ophthalmological assessment revealed bilateral lens subluxation so homocystinuria was suspected and later on confirmed after serum amino acids tests: homocysteine blood level 153.8umol/L, (normal 4-12mol/L) and methionine serum level 495umol/L (normal 43-223umol/L). The patient was started on treatment immediately: Betaine (Tri-methyl glycine) 5 gm/day orally, Folic acid 5mg/day orally, vitamin B6 (pyridoxine) 300 mg/day orally, Vitamin B12 (Hydroxy-cobalamine) 1000ug/week IM injection and restricted protein diet, but he had poor compliance mainly to diet. Later the diagnosis of CHU pyridoxine non-responsive type was confirmed by genetic study that confirmed homozygous mutation of c.1006C>T (p.R336C) in CBS gene.

At the age of 9, he was found to have increased muscle tone with exaggerated deep tendon reflexes in both lower limbs. A brain CT scan showed diffuse reduced attenuation of the white matter noted all over the brain parenchyma including the cerebellar white matter sparing of the overlying cortex and basal ganglia (Figure 2). A brain MRI was requested to confirm the findings but patient traveled abroad for bilateral lens implantation. The patient was evaluated again at the age of 13 years. At that time he was a full time student, with learning problems, speech and language difficulties.

He was able to walk, run, and go up & down stairs independently, and was independent in activities of daily living. IQ test revealed the following: verbal reasoning 37 (Average), visual abstract reasoning 36 (average), quantitative reasoning 31 (average), short term memory 25 (average) and overall IQ 59 (mental retardation-mild). Brain MRI at that period showed diffuse increased signal intensity on T2 and FLAIR of the cerebral per ventricular white matter bilaterally in a symmetrical pattern, there was also increased signal intensity of the cerebral white matter bilaterally on diffusion weighted images. No evidence of intracranial hemorrhage identified. The ventricles and extra axial CSF spaces appeared unremarkable. There was a focal area of cystic changes noted in the right cerebral per ventricular white matter keeping with an old insult (Figure 3).The MRA of the cerebral vessels showed no radiological evidence of vasculitis. The tortuosity of the optic nerves noted bilaterally.

Case 2

A 17 year old girl was diagnosed with classical homocystinuria at the age of 6 years. The diagnosis was suspected for the first time due to incidental finding of bilateral lens dislocation. Homocysteine level at diagnosis was 173.1umol/L and methionine level was 622umol/L. Later CHU pyridoxine non-responsive type was confirmed by isolation of c.1006C>T (p.R336C) CBS gene mutation. Family history reported no parental consanguinity. The patient had normal neonatal, infantile, and early childhood stages. On examination (age 6 years), she had arachenodactyly, limited cognitive function, speech was normal, and no abnormal neurological findings were detected .I.Q test was refused by parents. Soon after the diagnosis, she was started on medication: Betaine, Vitamin B6 (pyridoxine), folate, vitamin B12sub> (hydroxycobalamin) IM injections, and restricted diet but the patient was not compliant. Hearing assessment was reported as normal and she was followed up by ophthalmology for abnormal vision.

At the age of 7 years, the patient was admitted to the pediatric ward with one month history of intermittent, generalized, compressing type headache that was not associated with vomiting or nausea. A brain CT reported as exaggerated white matter hypo density of the supra tutorial brain symmetrically involved both hemispheres with no focal areas of infarction or hemorrhage (Figure 4). A Brain MRI done in the same period also revealed bilateral symmetrical diffuse white matter abnormality characterized by poor myelination. Electromyography and Nerve Conduction Study were normal. Echocardiogram was requested showed mild mitral valve prolapse with no hemodynamic consequences. Patient was discharged on oral aspirin with follow up in neurology and metabolic clinics.

Two years later a follow up evaluation in the neurology clinic, the patient continued to complain of infrequent bouts of headaches that were relieved by Aspirin. Neurological exam was normal at that time. So a follow up MRI head was requested, it showed stationary course with no newly developed lesion (Figure 5). Echocardiogram showed mild mitral valve prolapse with mild mitral regurgitation.

In 2008, sleep and a wake EEG was normal. A repeated MRI head in 2009 was reported as no new changes from previous study. Latest MRI brain done at age of 15 years showed no significant white matter abnormality visualized, no evidence of significant brain atrophy and with resolution of the previously reported white matter changes (Figure 6).

Case 3

A 15 years old girl was diagnosed at age of 3 years and 10 months as a case of classical homocystinuria due to Cystathionine Beta-synthase deficiency in early childhood, based on blood and genetic work up. Later the diagnosis of CHU pyridoxine nonresponsive type was confirmed by genetic test that identified c.1006C>T (p.R336C) CBS gene mutation. Family history revel no parental consanguinity. She was started on medication (Betaine powder 4gm Po twice daily, folic acid 5mg Po twice daily, vitamin B6 100mg Po twice daily, vitamin B12 injection 1mg IV once every 2 weeks, Aspirin 100mg Po once daily) and diet restriction, but had poor compliance. EEG was done routinely and showed abnormal bioccipital foci of spikes without clinically evident seizures.

Further EEG studies at age 6 and 8 years showed no changes.

MRI brain at the age of 5 years and reported as normal. At age of 8 years, a follow up brain MRI was reported abnormal and showed diffuse white matter abnormality with predominant per ventricular distribution (Figure 7). One year later, a repeated brain MRI showed bilateral symmetrical white matter hyperintense signals in T2 sequences mainly involving the subcortical white matter and Centrum semi vale region (Figure 8). A follow up brain MRI at 13 years of age revealed subtle high T2 signal noted bilaterally in the frontal and parietal white matter there were no gross white matter changes seen, there was no evidence of cerebral or cerebellar atrophy (Figure 9).

The patient also had regular follow up with ophthalmologist for myopia and was prescribed glasses. She was followed up by orthopedics for thoracolumbar scoliosis. Hearing assessment was normal. Cognitive assessment (I.Q) test score was 82, which is in the low average level.

At the age of 14 years, the patient had a visit to Accident and Emergency complaining of recurrent morning headache; however, her neurological examination was reported normal as well as the rest of her systemic evaluation.

Case 3

A 32 year old male, diagnosed with classical homocystinuria at the age of 10 years. He was born by vaginal delivery after uneventful pregnancy with a birth weight of 3.5 Kg. The patient had history of failure to thrive, and developmental delay mainly in speech and language skills. At 4 years of age his weight was below the 5th percentile for age and sex. There was also a history of bilateral inguinal hernias that were surgically corrected.

At the age of 6 years he presented with severe left eye pain, vomiting, and poor vision. Examination of the left eye showed dislocated lens in the anterior chamber, small pupils, high intraocular pressure >40 mmHg as well as dislocated lens of the right eye. Based on clinical findings of long face, high arched plate pectus carinatum and skin abnormalities he was diagnosed as: Marfa syndrome with recurrent attacks of bilateral dislocation of the lenses of both eyes and severe secondary left eye glaucoma leading to vomiting.

At the age of 10 years the patient traveled to USA for further ophthalmological assessment and management, where the diagnosis of classical homocystinuria was made based on a positive Cyanide Nitroprusside Test and serum amino acids test. Initially he was started on low protein diet and pyridoxine supplement. As he had pyridoxine non-responsive CHU, folic acid, Vitamin B12 injections, and Betaine were added, but he had poor compliance. In 2003, at the age of 20 years, c. 1006C>T (p.R336C) CBS gene mutation was identified.

The patient attended schools for children with special needs and he required educational support. When he was 16 years old, he underwent bilateral lens implantation, surgical correction of large left testicular hydrocele. He was also suffering from joint stiffness and kyphoscoliosis. The patient did not have previous MRI images as part of his diagnostic evaluation, however, at the age of 22 years, he was involved in a road traffic accident where he was a pedestrian. The collision resulted in head injury, chest trauma, right femoral shaft fracture complicated by fat embolism which required open reduction and internal fixation with three weeks of mechanical ventilation. During his hospitalization head MRI showed scattered white matter disease in a linear fashion along the distribution between the anterior and the middle cerebral arteries and scattered foci in the basal ganglia, the frontal white matter and few peripheral areas in the gray-white matter junction. The appearance is not specific. The history and the conspicuity of lesions on the diffusion-weighted images raised the possibility of fat embolism; the differential diagnosis includes ischemic white matter changes secondary to either homocystinuria or even as a complication of hypoxic injury.

The patient was discharged ambulating in good general condition, and Aspirin was added to his medications. He had a cardiology team follow up for trivial mitral regurgitation and mild aortic insufficiency. Laparoscopic cholecystectomy for gallstones and acute cholecystitis was done at 25 years old.

Discussion

In this report, cerebral white matter changes were detected by brain MRI in all the four patients with pyridoxine non-responsive classical homocystinuria whom had poor compliance to treatment and diet restriction. In case

The brain MRI was requested after he showed signs of upper motor neuron lesion.

In case had MRI due to frequent bouts of headaches.

MRI brain was requested as a follow up for abnormal EEG findings.

It was done to investigate the complications of a road traffic accident. The follow up MRIs images for case (2) and (3) showed resolution of the white matter changes.

Although brain white matter lesions unrelated to thromboembolic events are not classical manifestations of CHU, there is increasing evidence supporting that the presence of cerebral white matter changes might actually be part of the natural history of this rare disease. A 10 years Iranian experience of 20 patients with homocystinuria, neuro-imaging data showed that 13 (65%) patients had white matter involvement [10]. In 2002 Yaghmai et al. [11] reported massive cerebral edema without evidence of thrombosis occurred in a patient with pyridoxine non-responsive classical homocystinuria who was on Betaine treatment, the patient had poor compliance to diet restriction and very high methionine levels reached 3000umol/L [11]. Another study in 2004 described white matter edema after 4-6 weeks of Betaine treatment in a child with cystathionine beta-syntheses deficiency [12]. Reversible white matter changes were also reported by Vatanavicharn and Brenton et al. [7,13]. Regular MRI follow up in a 21 years old male with pyridoxine-nonresponsive CBS deficiency was used to document reversible cerebral white matter lesions in correlation to methionine levels [14].

The underlying cause of cerebral white matter changes in patients with classical homocystinuria is still not well understood whether it is a complication of the condition or as a side effect of the medications. Even though Betaine therapy was claimed to be the culprit by some authors [11,12,15], white matter changes were reported in a 4 year old boy just prior to the diagnosis of classical homocystinuria and starting treatment. His MRI changes were normalized a year after starting treatment including Betain [13]. In addition hypermethioninemia with levels as high as 1000umol/L or higher was a consistent finding in all reported cerebral white matter changes in patients with CHU [7,11-14] regardless of Betaine use. As Betaine acts on conversion of homocysteine to methionine through an alternative pathway (Figure 1), it will worsen the hyper methioninemia especially in poorly compliant patients to methionine dietary restriction. Another controversy is whether the underlying pathophysiology of the white matter changes is due to demyelination process [7] or intramyelinic edema [14,15].

Leukodystrophies have been documented in different amino acids disorders and those are due to many different mutations. An in-depth analysis of the mutations involved in previous and future case studies of white matter changes related to homocystinuria could shed light on another way where neurological deficits in CHU patients can be predicted and perhaps prevented. Linking different CBS gene mutations and the degree of pyridoxine responsiveness to the severity and the prevalence of cerebral white matter changes can be worthwhile.

Summary

In summary, our report confirms the finding of cerebral white matter changes in poorly controlled patients with classical homocystinuria that is most likely due to hypermethioninemia. Additionally we speculated that such complication is more likely to occur in patients with the Pyridoxine non-responsive type, supported by previously reported cases [7,11,12,14]. Unlike other leukodystrophies white matter changes in most classical homocystinuria cases are reversible, so early detection is essential as it may prevent serious complications such as brain edema.

Conclusion

Our report supports the hypothesis of hypermethioninemia rather than Betaine treatment as the cause of the white matter changes. Hypermethioninemia was documented in all our patients with levels ranging between 600->1000umol/L. The high methionine levels are most likely due poor compliance with treatment, especially the diet. We observed in two of our patients that when blood methionine levels dropped because of better compliance, previously seen brain white matter changes were reversible.

Our study opens the door for further research for better understanding of the natural disease progression and the longterm sequel (e.g. cognitive and learning abilities) of white matter involvement especially in non-treated or missed cases. Moreover, studies should be conducted to determine if methionine levels correspond to the appearance of cerebral white matter changes, their progression and resolution./p>

We stress on the importance of family/patient education to improve compliance with medications and follow the dietary restriction. Clinicians should consider performing brain MRI images at diagnosis and follow up studies for patients with classical homocystinuria who have poor adherence to diet restriction with rising methionine levels even in the absence of new neurological findings.

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Social Skills Training for Autistic Children: A Comparison Study Between Inclusion and Mainstreaming Education-Juniper Publishers

Abstract

The educational institution is an ever evolving entity. With the passage of P.L.94-142 [Education for All Handicapped Children Act] in 1975, the educational system was faced with the challenge of including all students with disabilities into the general education setting. Yet, millions of students continue their education in separate settings or in isolated facilities within districts [mainstreaming education]. Significant amounts of research indicate that separate special education programs have not had the positive impact originally anticipated for students. Research also indicates that isolated programs have not prepared students adequately for their futures.

Abbreviations: IDEA: Individuals with Disabilities Act; LRE: Least Restrictive Environment; VCSSO: Ventura County Superintendent of Schools Office; CARS: Childhood Autism Rating Scale; IEP: Individualized Education Plan; SEEC: Social-Emotional Early Childhood; WMS: Walker-McConnell Scale; UCSB: University of California; Santa Barbara; UCLA: University of California, Los Angeles

Chapter 1

Introduction

The individuals with Disabilities Act [IDEA] and the Least Restrictive Environment [LRE] requirements have been upholding in a series of federal district court decisions. These court decisions affirm the right of placement for students in the general education setting when educational benefits for the student are apparent [1].

The first premise of IDEA focuses on the right for all children to benefit from a free appropriate public education with appropriate supports and services, regardless of any disability. A second key premise is that all children have a right to a continuum of services and placements to meet their individual needs [2] The practice of educating children with and without disabilities in heterogeneous classrooms is referred to as inclusive schooling or commonly referred to as inclusion.

Inclusion is far more than the physical placement of a student with special needs in a general classroom. Inclusion involves a philosophy in which a school system allows for a variety of placements that offer the conditions under which every individual feels safe, accepted, and valued and is helped to develop his or her affective and intellectual capacities.

According to [1] there are some central differences between Full Inclusion Education and Mainstreaming Education:

Research has documented that non-handicapped peers can be effective in teaching social skills for students with autism. The most efficient methods for addressing the students with autism in inclusive settings include appropriately structured play activities. This efficacy is based upon peers’ training, and when the teachers actively prompt and then reinforce the interactions between the student with autism and the peers [3-5]. Consequently, there is currently a strong educational movement to integrate students with autism and other disabilities with their general education peers [6].

Moreover, research suggests that successful integration depends on the careful planning, development, and implementation of programs that emphasize both the academic and the social needs for students with Autism [6-9].

According to [8] social skills training have been a widely used intervention with children and adolescents. Social Skills Training is a process to remediate social skills deficits in children with emotional and behavioral disorders in order for them to attain social competence. The interest in social skills training with children is the relationship between early peer rejection and negative social adjustment. Social skills training programs are designed to teach pro-social skills. Appropriate social skills allow an individual to achieve three goals: [a] development of positive interpersonal relationships, [b] ability to cope with expectations of various social situations, and [c] execution of effective communication in social situations [8]. Contends that most contemporary approaches have been divided into four approaches: [a] the social skills approach, [b] the social problemsolving approach, [c] the social perspective taking, and [d] the selfcontrol training. Social skills in autistic children have always been a unique challenge. The question is whether social skills training in inclusive education programs are beneficial in improving social relationships and decreasing problematic behaviors.

Children with disabilities lose many opportunities for pleasurable experiences and friendships because of the misconceptions adults and the children’s peers have about them. Philosophies on how to teach children with special needs have changed since Public Law 94-142 was passed. The philosophies have ranged from completely segregated schools and classrooms, to partial participation, to partial mainstreaming, to peer tutor programs, to reverse mainstreaming, or to full or partial inclusion. Often, the only difference between philosophies is found in the definition of the different programs.

According to [10] she believes that it is clear that the children with disabilities are the ones who are often the forgotten factor when philosophies clash. Too many children have lost or are loosing the opportunities of meeting their typically developing classmates while the debate ranges around them. Research shows that exposure to typical peers enhances social development; allows for opportunities to model positive role models in the classroom, the playground and in the community; elevates selfesteem; and educates typically developed children about their disabled classmates. With training, negative behaviors decrease in the presence of positive behaviors and increase, or stay the same, without support or training for the child with the disability or regular education classmate. Children with disabilities should be placed in settings where the positive behaviors can be modeled and training can occur. This is in the regular education setting with full inclusion programs.

The likelihood of failure is greater when the child with the disability is placed within the regular education setting with no backup support, no specialized training of the teachers, and no education of his or her typical classmates. Children in regular education classes tend to be overly critical. They often have negative feelings and offer no opportunities for friendship to the disabled child if they do not understand the reason for the behaviors. Such children with disabilities, such as autism often appear to be physically and intellectually at age-level, but can have bizarre and surprising behaviors resulting from their disability that can alienate other children [8] Research shows that when regular education children receive information about the disabilities, are given the chance to act as “peer tutors” or “buddies”, and have full support of their teacher in times of confusion and frustration, the acceptance of the child with the disability increases dramatically [11].

The full inclusion program offers the regular education student the opportunity to learn about children with disabilities, specifically, children with autism. Teachers and staff receive training, information and hands-on demonstrations to aid in their inclusion program. The students in the regular education settings also receive information about the strengths and weakness in all people. The goal in offering information to the children is to build future peer tutor programs; offer friendship clubs; enhance the knowledge of the children and staff about disabilities; and to improve the lives of children who have traditionally had little or no opportunity for social involvement [10]. Consequently, social skills in autistic children in full inclusion programs can dramatically improve over children in mainstreaming programs.

The purpose of the study is to compare the effectiveness between inclusion and mainstreaming education in obtaining better outcomes in social skills for autistic children ages 3-8 years. Autistic children and their families deserve to be given the most beneficial treatment because of the far reaching detrimental effects of their condition. Continued field research on the effectiveness of inclusion education to obtain better outcomes in social skills for autistic children will provide essential information to clinicians, educators, social workers and researchers.

Chapter 2

Literature Review

The literature on the following topics is reviewed in this chapter: Changes in the Population of Persons with Autism and Pervasive Developmental Disorders in California’s Developmental Services System, Definition of Autism, Social skills training, Inclusion and Mainstreaming Education, Benefits of Inclusion Education for Children with developmental disabilities, and Treatment for Autistic Children.

California’s Developmental Services System

Findings

From December 1998 to December2002, the population of persons with autism in California’s Developmental Services System nearly doubled. For the four-year-period from December, 1998 to December, 2002, there was a net increase of 10,017 individuals [a 97% increase] in the autism caseload. At the end of December 1998, there were 10,360 persons with autism Codes 1 and 2 served by all 21 regional centers, and by the end of December 2002, the total was 20,377. Additionally, comparing the figures from December 1987 to December 2002, there was a 634% increase in autism [Codes1 and 2] in the 15 years from 1987 to 2002.

Age Distribution

Interestingly, this report shows a shift toward younger persons with autism [Codes 1 and 2] between 1987 and 2002. In 1987, the autism population served by regional centers totaled 2,778 persons. The highest percentage of persons in 1987 was in the 20 to 24 year age-range. By the end of 2002, when the autism population totaled 20,377 persons, the greatest number of persons [4,282] shifted to children in the 5 to 9 year age-range. By 2002, 70% of all persons with autism in the regional center system were under 15 years of age, compared to 35% in 1987.

Ethnicity

This report also shows shifts among ethnic groups in the number and percentages of persons with autism between 1987 and 2002. Relative to the entire population of persons with autism, Asians and Hispanics increased the most in the 15-year interval between 1987 and 2002. Relative to the entire autism population in 2002, the Asian and Hispanic proportion more than doubled compared to 1987.

Gender

In the 15-year comparison, the report shows a 5% proportional increase in males with autism compared to females. In [12] 2,140 individuals with autism were male [77.03%] and 638 individuals were female [22.97%]. By the end of December 2002, 16,675 individuals with autism were males [81.83%] and 3,702 were females [18.17%].

The Department’s 1999 Report on Changes in the Population of Persons with Autism and Pervasive Developmental Services System reached two general conclusions: [a] the number of persons with autism continues to increase dramatically, and [b] autism is and will almost probably continue to be the fastest growing disability served by the regional center system [California Department of Developmental Services, 2003].

Definition of Autismw

Autism is a developmental disorder that is behaviorally defined [10]. Autism is defined in the DSM-IV [2000] as a “pervasive developmental disorder”, and it is one of the five subcategories of Pervasive Developmental Disorders. Autism is a disorder that manifests itself in infancy, severely affects the development of social interaction, communication skills, and behavior. It results in the presence of stereotyped behaviors, interests and activities. Typically apparent before age three, autism affects four times as many boys as girls and is found in families of all races, religious and social classes.

Autism is one of the most prevalent developmental disorders, affecting 1 in 1000 births to 2 in 1000 births if the full spectrum of autistic behavior is included —autism, Pervasive Developmental Disorder Not Otherwise Specified [PDD NOS], Asperser’s Disorder, Rhett’s Disorder, and Childhood Disintegrative Disorder [10]. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. Autistic Disorder is sometimes referred to as early infantile autism, childhood autism, or Kenner’s autism [DSM-IV-TR] [11- 13]. Autism is also viewed as an expression of an identified neurological disorder.

The exact cause or causes of autism are currently unknown; although recent research shows a spectrum of impairments at both the anatomical and microscopic levels. There is no specific clinical answer to the definition of autism since every case is unique. It is important to consider the degree of heterogeneity possible among people with autism. Individuals with autism will vary in the number of symptoms they present, the severity of those symptoms, the degree of cognitive impairment they will experience, and the number and type of associated medical problems they will have. The individual’s involvement in appropriate treatment and education also needs to be considered; although the majority of individuals with autism will require life-long support services, research is indicating that early, behaviorally based intervention and placement in highly structured, family-focused and community-based services is critical to obtain the best possible outcome [14,15]. And it is also important to consider that autism is a disorder of development and, as such, will affect the individual in different ways during different stages of development [16].

According to [16], the autistic disturbance is generally considered to include some combination of the following symptoms.

Autistic children exhibit a profound failure to relate to other people, which is often apparent from birth. They may show an absent or delayed social smile, and may not reach upwards in anticipation of being picked up. Some children fail to form emotional attachments to significant people in their environment, for example, not showing distress when the mother leaves the room. Similarly, a child may play in the vicinity of other children without interacting or participating with them.

Autistic children commonly show various levels of impaired or delayed language acquisition and comprehension. Many autistic children are mute and others may show echolalia. Immature grammar, pronoun reversals, and/or inability to use abstract terms may also be apparent.

Many children show apparent sensory dysfunction, as if they do not see or hear some environmental events. They may exhibit under -or over responsiveness to touch, light, sounds, or pain. For instance, the child may not exhibit a startle response to a loud disturbance, but may respond to the sound of a candy wrapper, or may tantrum excessively every time a siren goes by.

Many autistic children show inappropriate and/or flat affect. They may not display appropriate facial expressions and may not exhibit fear in dangerous situations, such as crossing the street. They may respond to even simple requests with severe, prolonged tantrums. They may also laugh and giggle uncontrollably in the absence of apparent eliciting stimuli, or cry uncontrollably for hours.

Typically, autistic children will occupy themselves for hours with stereotyped, repetitive self-stimulatory behaviors, which serve no apparent purpose other than providing the child with sensory input. Commonly, self-stimulatory behaviors take the form of manipulation of hands or fingers in front of her eyes, eye crossing, repetitive, meaningless vocalizations [e.g. “aeh, aeh, aeh…”] suspending or spinning objects in front of the eyes, mounting objects, hand tapping, body rocking, and other stereotyped behavior. Such behaviors have been found to significantly impair learning in autistic children [17].

Autistic children often fail to develop normal, appropriate play. They may forsake toys altogether, preferring instead to spin a lampshade or flick a light switch on and off. Social play with peers may develop spontaneously, but usually does not.

Autistic children commonly show obsessive, ritualistic behaviors which have been characterized as a profound resistance to change in the environment or normal routines. Familiar bedtime routines, insistence on one type of food, one type of furniture arrangement, and particular routes to familiar places are examples of routines which, when altered even a minor fashion, can create extreme disruption in a child’s behavior. Table 1 summarizes some if the characteristics presented and associated with autism.

Neurological Disorders

By tradition, autism has only been diagnosed without the evidence of known neurological dysfunction. However, the prevalence of evidence now strongly suggests that autism may involve a neurological disorder [18-20]. In addition, recent evidence suggests that some impairment of auditory processing in the language-dominant hemisphere of autistic children may exist [21,22] suggest that the symptoms of autism could express some physical dysfunction within the central nervous system which remains to be characterized. Whatever the exact cause is, however, neurological improvement does appear possible with behavioral intervention [21]. Note. Some statistics are subject to debate and need further research.

Individuals with autism differ extensively from one another. Although they may exhibit different characteristics among those outlined above, all individuals with autism have underlying similarities of impairment in communication, socialization, interests, and behaviors. Severity of autism can range from very mild to quite severely impair. This can be confusing to many parents and professionals trying to understand the disorder of autism. However, parents and professionals need to remember that all individuals with autism can progress and learn when their programming is designed around their unique, specific needs [10].

Social Skills

One definition of appropriate social skills is that they are prescribed ways of behaving; they are expectations of particular groups as to how group members will conduct themselves in private and in public. Prescriptions for what is socially appropriate vary from community to community and society to society. Variations exist even within the tight circle of home, preschool, and neighborhood. But confusing choices often result, especially for young children. However, rather than attempting to define a term like social skills, the following list is considered according to [23]. The major social skills to be learned during the early years relate to getting along with others.

Interacting with children and adults, in a variety of ways, at home and away from home.

Trusting and enjoying known adults outside the immediate family.

Recognizing and protesting inappropriate advances from known or unknown adults within or outside the family.

Attending to self-care needs at home and in public places with consideration of others.

Sometimes initiating play ideas with children, other times, following children’s lead.

Participating in group activities through listening, taking turns, and contributing to group effort.

Sometimes putting aside individual needs and interests so the needs and interests of the group may be met.

Working and playing independently as well as operatively; learning to be alone without feeling isolated or rejected.

Using language as the powerful social tool it is for persuading, defending, reasoning, explaining, solving problems, and getting needs and preferences attended to.

Children with developmental disabilities, such as autism, like all young children, need to learn to get along with others. To do this, they must learn appropriate social skills. Such learning may be more difficult for children with developmental problems. Like all other skills, social skills are dependent on every other area of development. Notwithstanding, children of all developmental levels can master basic social skills as prescribed by their respective families, schools, and communities [23].

Inclusion and Mainstreaming Education

Inclusion differs from mainstreaming in that mainstreaming provides disabled students the opportunity to be placed in regular class- with other disabled peers, based on the student ability to keep up with work assigned, with some modifications. Instructional support and related services are typically provided outside the regular education setting. Integration, a term popularized in the 1980s, was used to indicate the placement of a disabled child in a special class, in a typical school, where the student could participate in some activities with non-disabled peers. Special education services were usually provided in a special education class. This fragmented approach caused children to become lost in the system [24].

Inclusion refocuses the LRE [Least Restrictive Environment] provision to keep a student in the class that he or she would attend if not disabled. Services are provided in the regular classroom unless the nature and severity of the student’s individual educational needs are such that a more restrictive setting must be considered for the child to be provided an appropriate education. An educational debate is ongoing regarding inclusive education of disabled children. This conflict involves two basic groups: [1] parents, teachers, and administrators who support inclusion; and (2) representatives of these groups who are against inclusion as an educational philosophy and practice [25].

Inclusion means that children with special needs attend preschool, childcare, and recreational programs with their typically developed peers. However, inclusion is not about a place, or an instructional strategy, or a curriculum; inclusion is about belonging, being valued, and having choices. Inclusion is about accepting and valuing human diversity, and providing the necessary support so that all children and their families can participate in programs of their choice. “Inclusion is a right, not a privilege for a select few”[Roberti V. Board of Education in Clementon School District, 1993]. The call for inclusion is coming from families, professional organizations, and advocacy groups [26].

Benefits of Inclusion Education

Benefits to Children with Autism

Children with autism have pronounced impairments in social and communication development that hinder their interactions with peers and family members. When a child with autism does not have access to adaptive role models, progress toward improving social and communications skills is often hampered. Regular education can offer valuable opportunities for social interactions with peers. However, placement in regular education alone does not ensure success [10]. Children with autism require supports to help them develop and generalize necessary social skills. With adequate supports in place, significant improvements in social interactions can occur [10]. Thus, inclusion education offers a door for better outcomes in social skills for children with autism.

Benefits to Children to Typical Children

Typical peers also benefit from participation in an inclusion program by developing a heightened awareness of the needs of children with disabilities. This can lead to greater sensitivity toward others and acceptances of the relative strengths and weakness that people have. Many parents acknowledge these benefits of inclusive programs [24].

Benefits of peer tutoring/social skills programming

Teachers have long recognized the additional benefits that peer influence has on teaching academics and on the student’s self-esteem. Implementing formal peer tutor programs with a strong foundation of social skills, the students with disabilities benefit. Students who experience difficulty with peer interactions or reciprocal conversations are presented with numerous opportunities in which peers frequently and repeatedly request appropriate responses from them. This provides the students with the best environment to develop skills in both the social and language domains under the guidance of a teacher.

With consistent and frequent exposure to peer programs, teachers and parents report that students gain increased language production, decreased solitary play, and increased appropriate social skills. Teachers and parents have begun to recognize that it is extremely difficult for adults to teach age-appropriate social skills to a child. However, children often readily learn these skills from another child, making peer tutor programs and social skills training important, especially during the school years [10]. These programs are well worth investigating for any professional interested in social and language difficulties in autism.

Treatment for Autistic Children

Several studies reveal that involving peers in social skills interventions provides children with autism the opportunity to observe, imitate and learn from the social behaviors of their typically developing peers [27]. However, to increase the social awareness of these children in the inclusive setting, educators must carefully design peer interventions to take into account the range of special characteristics found in children with autism. The purpose of this topic is to review two recent articles that focus on teaching peer social skills to children with autism and to note some practical implications of this research for professionals interested in social skills training in autism.

According to one of the first investigations in the autism social skill literature performed by Free [28], it was utilized naturalistic behavioral observation to clarify the social behavior of children with autism and their typically developing peers, and to compare each group’s behavior in the same setting. Participants were five children, four male and one female, all with the diagnosis of Autism Spectrum Disorder who were enrolled in inclusive classroom settings. Once or twice per week, examiners observed and recorded three target behaviors for each group: [a]the number of minutes appropriately engaged in a task, [b]the number of stimulus items used while task-engaged and [c] the number of social-communicative interactions emitted.

Results

Indicated that children with autism used the same number of task objects as comparison children; however, the children with autism spent far less time engaged with each item. Overall, children with autism were engaged in tasks only one-half as long as contrast children. Additionally, the children with autism rarely engaged in social-communicative interactions with other children, whereas comparison children did. However, the amount of social interaction between autistic and comparison children was found to be similar to previous reports regarding their rates of communication with adults.

Consistent with the extant autism literature, these results provide strong naturalistic evidence that children with autism have severe deficits in the area of peer interaction skills. It is hypothesized that children with autism may become more willing to interact with others if they are given an opportunity to practice newly acquired social skills with normally developing classmates also placed in the skills training program. Since inclusion is the ultimate goal of special education, results of this study suggest systematic and long-term social skills training should be considered an integral part of inclusion programs for children with autism.

In other study performed by Kemps et al. [18] it was examined the contributions peers can make to the generalization of social behaviors for children with autism through peer social skills programs.

Two investigations were completed, and each examined the role of peers when trained in explicit interaction strategies with children with autism during and after specific treatment. Generalization of these skills for target and peer participants was a particular focus of study. Participants for study 1, which examined the effects of generalization on social skills, cooperative learning and peer training, were 5 students with autism and 51 general education peers. Three peer groups were derived for the analysis of generalization:

Those who participated in cooperative learning groups with children with autism,

Those in social skills groups with children with autism, and

A group of peers familiar with the students with autism but who did not receive training. Results indicated that during cooperative learning groups with peers, time engaged in interaction increased from 30 to 191 seconds, a rate similar to what was found for typically developing peers. However, during social skills training groups, students with autism increased their peer interaction time from a range of 7-56 to 152-262 seconds.

Study 2 included 34 students with autism and approximately 130 peers who participated during the initial year and 120 more during the final probe year. Students received a variety of peer mediation programs:

Social skills groups,

Lunch buddy groups,

Recess buddy groups and

Tutoring programs. Peers and target students received direct instruction in the use of skills within the context of each activity.

Results indicated that for students with autism improvements were made in social interaction skills with non-disabled peers. Average interaction duration time between students with autism and trained peers [393 sec] was longer than with familiar peers [301 sec], which was longer than the time spent interacting with stranger peers [246 sec].

These findings are particularly important for school psychologists because they suggest the practicality of peer mediation programs to support elementary classrooms for children with autism. Second, these results indicate that social skills programs alone are not as efficient as a program that includes both academic and social mediation, and that including trained peers in these cooperative learning programs is essential for increased social interactions for students with autism placed in general education. Statement of the Problem. The problem is to examine whether inclusion education for autistic children is more effective than mainstreaming education. The children in this study will be 3-to 8-year-olds diagnosed with Autism. The children will be enrolled in inclusion programs and mainstreaming education for the past 12 months of school calendar year.

The specific objectives of the study are

To obtain the degree of change in social skills in children participating in the scoring of social skills through testing.

To identify the degree of change in social skills in children participating in the scoring of social skills with the initial evaluation of the school and the results of the testing.

To compare the effects of the inclusive and mainstreaming education in their social skills.

To compare the changes in the population of persons with autism and pervasive developmental disorders in California’s Developmental Services System from 1987 through 2002.

To compare the financial effects of social training education and the treatment of autistic individuals who did not receive social skills education or inclusion education during childhood —untreated autistic expenses.

Research Questions

The research questions of this study were as follows:

Will autistic children in inclusion programs have higher levels of social skills than mainstreaming children?

Is there a relationship between improvement of social skills and inclusion education?

Will inclusion programs provide a financial reduction in educating autistic children compared to the treatment of autistic individual who did not receive social skills education or inclusion education during childhood?

Chapter 3

Methods

Participants

The first delimitation of the study is the profile of the participants. A total of 160 participants will serve as the base sample. Subjects will be enrolled for scoring if they meet three criteria: [a] only 3-to 8-year-old students; [b] participants will be currently enrolled for the last 12-months school calendar year within the Ventura County Superintendent of Schools Office [VCSSO] and the Ventura County Superintendent of Schools Special Education in the areas of Oxnard, Camarillo, Fillmore, Santa Paula and Ventura California; [c] the participants will be enrolled for the last school calendar year within the VCSSO in Pleasant Valley School District, Rio School District, Fillmore Unified School District, Briggs Elementary School District and Ventura Unified School District, Oxnard Elementary School District, and Santa Paula Elementary School District; [d]the participants will be enrolled for the last 12- months within the Ventura County Superintendent of Schools Special Education in San Miguel Preschool in Oxnard, Santa Rosa School in Camarillo, Phoenix School in Camarillo, Douglas Penfield School in Ventura, Dire School in Oxnard, Hollywood Beach in Oxnard, Valle Linda in Camarillo, and Phoenix - Los Nogales in Camarillo.

Measures

The clinical diagnosis of autism will emphasize emotional detachment, interpersonal isolation, impairments in communication and social skills, little toy or peer play, rituals, emotional vulnerability, and onset in infancy. The diagnosis of autism will be made prior to family contact with the project. Participants will be assessed in their development of their social skills by the initial Individualized Education Plan [IEP], the Child Autism Rating Scale [CARS], the Vineland Social-Emotional Early Childhood Scales, and the Walker-McConnell Scale of Social Competence and School Adjustment for the screening and identification of social skills.

The Individualized Education Plan[IEP]: Includes information relevant to the student’s performance in the areas of cognitive ability, academic performance, communication skills, motor skills, sensory, health, social and emotional, adaptive functioning skills, and vocational assessment. Psychological and related reports may also be included. These IEPs are written annually and are updated throughout the year. These documents are a part of the student’s permanent file. Some special education departments encourage paraprofessionals to read the IEP file [11].

The Childhood Autism Rating Scale [CARS] [Scholar et al., 1988]: is an individually administered instrument that consists of 15 behaviorally rated items designed for the identification and assessment of autistic children. The CARS is an observational instrument that can be used to reliably distinguish children ages 2 and over with the autistic syndrome from children with other developmental disorders, as well as to differentiate among levels of severity within the autistic syndrome.

The CARS was also designed to replace subjective clinical judgments with objective criteria based on empirical research. It can be used during observations of child behavior in a variety of settings, or may be used with information gathered from chart or record reviews. The CARS is composed of 15 4-point scales on which a child’s behavior is rated on a continuum from within normal limits [1] to severely abnormal [4] for chronological age. Total scores are used to categorize a child on a continuum ranging from non-autistic, to mild to moderate autism, to severe autism. The CARS is supposed to be an initial aid in the classification process. The scores are as follows: 16 rating scores: Relating to People, Imitation, Emotional Response, Body Use, Object Use, Adaptation to Change, Visual Response, Listening Response, Taste-Smell-Touch Response and Use, Fear or Nervousness, Verbal Communication, Nonverbal Communication, Activity Level, Level and Consistency of Intellectual Response, General Impressions, Total.

Internal consistency [coefficient alpha] is found to be .94. Interpreter reliability is .71, with a range of .55 [Level and Consistency of Intellectual Response] to .93 [Relating to People]. Test-retest reliability of CARS scores for 91 cases assessed 1 year apart resulted in a correlation of .88. Test-retest reliability of CARS diagnoses [i.e., non-autistic, mild-moderate autism, or severe autism] from the second to third annual evaluation resulted in a coefficient kappa of .64. The CARS has a correlation of .84. Validity of the CARS across different settings reveals a coefficient Kappa’s of .75 [parent interview vs. psycho educational testing], .86 [classroom observation vs. psycho educational testing], and .63 [case history review vs. psycho educational testing].

The Vineland Social-Emotional Early Childhood Scales [Sparrow et al., 1998] is an instrument designed to assess the social and emotional functioning of children from birth through 5 years 11 months of age. The Vineland SEEC Scales are a subset of items from the Socialization Domain of the Vineland Adaptive Behavior Scales, Expanded Form. The Vineland SEEC is designed to be individually administered through a semi structured interview with a respondent who is familiar with the child’s behavior. The test consists of three scales: Interpersonal Relationships, Play and Leisure Time, and Coping Skills that combine to yield a Social- Emotional Composite score.

Information on the reliability of the Vineland SEEC Scales is also presented in a clear and comprehensive manner. Internal consistency levels are adequate, with median values of the Interpersonal Relationships, Play and Leisure Time, and Coping Skills Scales ranging from 80 to 87. The internal reliability coefficients of the Scale Composite, across six age groups, range from 89 to 97 with a median value of 93. Adequate stability is also well documented with the vast majority of the component scale and composite score test-retest correlations falling between 71 and 79.

The Walker-McConnell Scale of Social Competence and School Adjustment [WMS; Walker & McConnell, 1988] was designed primarily for use in the screening and identification of social skills deficits among elementary aged children in school. The WMS is quickly administered and scored, and focuses on important domains of child functioning. Refreshingly divergent from most other rating scales of child behavior, the WMS is positively focused [i.e., it centers on skills rather than problems in both the item wording and the resulting scales].

The inter scale correlations reported for the national norm sample of .67, .74, and .67 are too large to support the case for separate subscales. The interpreter reliabilities reported are low to moderate, ranging from .11 to 74 [median = .49] for the subscales. Interpreter reliabilities for the total score are .53 and .62 for two samples of 13 and 17 severely disturbed children of elementary and middle school age, and .63 to .83 for a sample of 19 Head Start children ages 4 and 5 years. Test-retest reliabilities are moderate to high, ranging from .90 to 97 for a 2-week interval, and from .61 to .70 for a 6-month interval. High coefficient alphas are reported that exceed .90 for all grade levels for all scales, including the total score. No evidence of individual item reliability is reported.

Procedure

The data will be collected by means of an in-depth, semi structured interview and a brief demographic questionnaire of the student at the end of the interview. The interview protocol will be based on that of Koegel et al. [29] for the evaluation of the student’s current social skills, and the recollection of data information from the Individualized Education Plan [IEP]. Additionally, the participants will be assessed with the Walker-McConnell Scale of Social Competence and School Adjustment for the screening and identification of social skills deficits; and the Vineland Social- Emotional Early Childhood Scales [Vineland SEEC Scales] for the assessment of the social and emotional functioning of children. The Child Autism Rating Scale [CARS] will be applied for the identification and assessment of autistic children. Participants will be diagnosed with autism by either of the following professionals and/or institutions: The Tri-Counties Regional Centers, University of California, Santa Barbara [UCSB], University of California, Los Angeles [UCLA], a family neurologist, a family psychiatrist, and/or a family physician [30].

A preliminary meeting with the school districts and the teachers will be held to discuss the participation of the students in the study, the content of the inclusion and mainstreaming education, and procedures for incorporating this activity into their courses. By mid-January of 2006, parents will be informed of the study and will be asked to provide consent to participate.

On the first chosen day, teachers will be given the semi structured interview and a brief demographic questionnaire of the student at the end of the interview. Subsequently, the IEP for every student will be analyzed. On the second day, upon arrival at the designated classroom, the student will be given The Child Autism Rating Scale [CARS] for the identification and assessment of the different levels of autism in the participant. The lead facilitator will instruct the student with the procedural questions according to the administration manual of the instrument [administration time depends on the participant]. After the lead facilitator read the instructions, the student will proceed with the activities of the instrument.

On the third day, the student will be given the Walker- McConnell Scale of Social Competence and School Adjustment for the screening and identification of social skills deficits [5- 10min]; and the Vineland Social-Emotional Early Childhood Scales [Vineland SEEC Scales] for the assessment of the social and emotional functioning of children [15-25min].

For the initial interview on overall social skills [will be 1-very little to 7-very much], means and standard deviations will be computed for each group [inclusion and mainstreaming].

Students will be divided into two groups: [a] inclusion and [b] mainstreaming. This study will examine the higher levels of social skills with the two programs, inclusion and mainstreaming. Because higher social skills indicate better outcomes in socialization, a high mean is desirable.

Two-Way Analysis of Variance [2-Way ANOVA] between subjects will be conducted. This will be used to determine the significance of the main effects and the interaction at the .05 level. This study will show the interaction between the effectiveness of social skills in autistic children and the inclusion education. Three levels of autism are measured: [a] mild impact, [b] moderate impact, and [c] severe impact. Thus, by comparing the column means, we are answering the question of which program is more effective in general without regard to how the impact of autism is.

Hypotheses

The derivation of the hypothesis, the general research hypothesis and the specific hypothesis are presented in this section. This study will emphasize the recent trend toward inclusion in general education, there is an increased number of children with autism and other pervasive developmental disorders who are being educated in the same classroom settings as their normally developing peers. As a consequence, considerable attention has been dedicated to promoting effective intervention techniques to enhance peer social skills among children with autism. Teaching appropriate peer interactions is an integral element of a comprehensive behavioral program for children with autism [Taylor, 2001]. As children with autism grow and acquire the basic skills necessary to function effectively in a one-on-one inclusive setting, the need for peer interaction skills becomes apparent.

General Hypothesis

Autistic Students who receive inclusion education approach in preschool and elementary school will have better outcomes in their social skills than those who receive mainstreaming education approach.

Specific Research Hypothesis

Autistic students, ages 3 to 8 who receive inclusion education approach in preschool and elementary school within the Ventura County Superintendent of Schools Office [VCSSO] will have better outcomes in their social skills than those who receive mainstreaming education within the Ventura County Superintendent of Schools Office [VCSSO] Special Education Department.

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juniperpublishersanesthesia · 5 years ago

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The Conversion from Continuous Sufentanil Infusion to Oral Retarded Opioid Medication: Beware of the Equi-Analgesic Opioid Ratios - A Case Series-Juniper Publishers

Abstract

Background: Sufentanil has an outstanding place in clinical practice and one cannot think of surgery or intensive care therapy without it. However, the routine use of continuous sufentanil infusion may cause severe problems if stabilized patients are discharged from the ICU after surgical treatment and need to be converted to oral opioids.

Aim & method: Here we report our experiences with a series of six patients that we have converted from intravenous sufentanil to oral morphine.

Cases: In 6 cases, we report intensive care (ICU) patients after surgical or medical therapy, who received sufentanil infusion for analgosedation. The patients were between 45 and 68 years old. It can be demonstrated that the optimal dose of sufentanil can be converted to minor doses of oral medication than expected from the calculated equi-analgesic ratios. Despite of lower oral opioid medication pain levels did not increase after conversion.

Conclusion: We recommend to begin opioid conversion with 10% of the calculated equivalent dose of intravenous sufentanil when converting to oral long-acting morphine and afterwards to further adapt the dosage.

Introduction

Since its development in the late 70s, sufentanil has an outstanding importance in clinical practice and one cannot think of surgery or intensive care routines without this treatment. The substance delivers a much higher potency than its parent drug fentanyl with an expanded therapeutic range [1,2]. From the beginning of its clinical use, sufentanil was the intravenous opioid of choice for hemodynamically instable patients [3]. Due to its outstanding hemodynamic stability resulting from a minor impact on cardiac index, left ventricular ejection fraction and heart rate [4], sufentanil is broadly used for critically ill patients in cardiac and non-cardiac surgery. In comparison with fentanyl, it has a shorter context-sensitive half time that results in better controllability [5] and predisposes the use of sufentanil in extended cases and for continuous infusion in intensive care.

The decoupling of analgesia and respiratory depression [6] is another reason for preferring sufentanil during weaning of mechanically ventilated patients or in those with spontaneous breathing. However, the routine use of continuous sufentanil analgosedation in the ICU may result in the problem that stabilized patients are still not free of pain or suffer from chronic pain and thus need to be converted to oral opioid medication, if discharged from the ICU after surgical or medical therapy. For example, common dosage of 20μg of sufentanil per hour has to be substituted by oral opioids as the patient should be transferred to the floor. The calculated equivalent dose for oral substitution would be 1440mg morphine per day, which is, of course, not practicable.

The following cases should demonstrate that sufficient pain therapy can be achieved also with significantly lower morphine doses. We report here six cases in which the hospital pain service was consulted to assist non-anesthetic intensive care units in the conversion from intravenous sufentanil to oral medication.

Case Presentation

Case 1: Patient J.S., male, 44 years old, weight 170kg, height 175cm; septic shock with multi-organ failure

The patient who suffered from arterial hypertension, atrial fibrillation, type-II-diabetes mellitus and morbid adipositas was admitted due to severe and rapid deterioration of his general condition. He developed a septic shock with subsequent multiorgan failure including renal insufficiency requiring dialysis, and liver failure. Furthermore, he developed a cardiogenic shock with a left ventricular ejection fraction of about 10%, and required cardio-pulmonary resuscitation (CPR) as ventricular fibrillation occurred.

After improvement and when the patient was able to be transferred to the floor, he received sufentanil infusion with 25μg per hour. The patient reported pain scores between NAS four and eight with burning quality. Pain therapy was converted orally to long-acting morphine (MST®, Mundipharma Ltd., Limburg an der Lahn, Germany) 3x100mg and 30mg mirtazapine (REMERGILSolTab®, MSD Sharp & Dohme GmbH, Haar, Germany) in the evening and short-acting morphine(Sevredol®, Mundipharma Ltd., Limburg an der Lahn, Germany), 20mg up to six times daily on demand. After a stepwise reduction of the morphine dose down to 3x30mg long-acting morphine per day and 30mg of mirtazapine, the pain service could sign off after seven days.

Case 2: Patient P.M., male, 63 years old, weight 97kg, height 180cm; serial rib fractures with pleural empyema

*This patient received additionally transdermal fentanyl (Durogesic SMAT 75pg/h)

The patient suffered from a traumatic left-sided rib series fracture and developed pneumonia and a pleural empyema while under conservative therapy. Secondary diagnoses comprised arterial hypertension, COPD, type-II-diabetes mellitus and chronic renal insufficiency. After surgical intervention and intensive care therapy with prolonged weaning, the patient was presented to the pain service for conversion to oral opioids. The current pain therapy was 20μg/h of i.v. sufentanil (Table 1). The patient was switched to 3x60mg long-acting morphine sulphate (MST®, Mundipharma Ltd., Limburg an der Lahn, Germany) and 15mg mirtazapine (REMERGIL SolTab®, MSD Sharp & Dohme, Haar, Germany) in the evenings; additionally Sevredol® 20mg up to eight times daily was prescribed, if VAS exceeded 5. After a stepwise reduction of the morphine dose down to 3x30mg with an evening dose of 15mg mirtazapine, pain service consultation ended after four days, the patient being satisfied at VAS <4.

Case 3: Patient S.L., female, 53 years old, weight 146kg, height 170cm; sepsis with multiple arterial emboli

The patient was primarily treated for a sepsis with unknown focus and suffered from morbid adipositas, a history of hypertension and type-II-diabetes mellitus in the intensive care unit. During the clinical course, both legs had to be partially amputated due to multiple arterial emboli; the right leg below the knee, the left leg above.

Under sufentanil infusion of 40μg/h, the patient was presented for conversion to oral therapy. The initial regime comprised 3x100mg of long-acting morphine with pregabaline (Lyrica®, Pfizer®, Berlin, Germany), 2x150mg, and Sevredol®, 20mg up to 6 times daily, if VAS exceeded 5. The consultation ended after five days, with morphine dosage reduced to 3x30mg of long-acting morphine and pregabaline 2x150mg. The patient was satisfied at VAS <3.

Case 4: Patient K.K., male, 58 years old, weight 104kg, height 180cm; osteomyelitis and acute renal failure after coronary arterial bypass grafting (CABG) surgery

The patient was treated for sternal osteomyelitis and acute renal failure after coronary arterial bypass grafting. In addition, the patient suffered from arterial hypertension, peripheral arterial vascular disease, hyperlipoproteinemia, COPD (GOLD III) and had been treated previously for laryngeal cancer with laryngectomy and bilateral neck dissection. At presentation to the pain service for conversion to oral medication, the patient received 20μg/h sufentanil with additional transdermal fentanyl (Durogesic SMAT 75μg/h, JANSSEN-CILAG, Neuss, Germany), which the patient had already before surgery. Pain scores of VAS=6 with peaks at VAS=8 were reported. The patient was converted to long-acting morphine 3x100mg/day and additionally with 3x100mg carbamazepine (Carbamazepin HEXAL®, Salutas Pharma, Barleben, Germany) with opportunity of receiving supplementary 20mg Sevredol®, up to 8* per day. After reducing long-acting morphine to 2*50mg with carbamazepine 3*300mg, pain service consultation ended after six days, the patient being satisfied at VAS=3-4.

Case 5: Patient R.S., male, 66 years old, weight 80kg, height 178cm; Multiple Myeloma and ARDS

The patient needed mechanical ventilation support for acute respiratory insufficiency under pre-existing multiple myeloma. During the clinical course, the patient developed acute renal failure requiring dialysis, aspiration pneumonia and critical illness polyneuropathy. After prolonged weaning, an apparently pain stricken patient was presented to the pain service receiving 20μg/h sufentanil, for conversion to oral analgesics.

At pain levels of VAS=5 and peaks of VAS=9, initially long- acting morphine 3*100mg/day with 150mg pregabaline (Lyrica®, Pfizer, Berlin, Germany) in the evenings was prescribed, with the possibility of additionally receiving 8*20mg Sevredol® per day. After stepwise reduction of morphine dose to 2*20mg/d of long-acting morphine and 150mg pregabaline in the evenings, the patient was discharged from the ICU with VAS=3 and the patient was discharged with 2*10mg/d long- acting morphine and with 150mg pregabaline.

Case 6: Patient K.B., male, 62 years old, weight 60kg, height 160cm; hemorrhagic shock after bypass surgery of the femoral artery

Following bypass surgery of the femoral artery with secondary hemorrhage and hype volemic shock, the patient developed an urosepsis. Preexisting diagnoses were peripheral vascular disease, arterial hypertension, type-2-diabetes mellitus and stage-III-renal insufficiency. After stabilizing the patient and planning for discharge to the ward, pain service was consulted for conversion of i.v. Sufentanil, 20μg/h, to oral medication.

The patient described pain as having piercing/stabbing qualities at VAS=3, peaking at VAS=9. After a stepwise reduction of initially 3*100mg/day long-acting morphine with mirtazapine 15mg for the night, the patient was discharged from the ICU with 3*60 mg/d long-acting morphine with afore mentioned mirtazapine at VAS=1.

Discussion

In clinical practice, sufentanil is indispensable for anesthesia and intensive care therapy. However, a conversion from continuous sufentanil infusion to oral opioid medication is essential for discharge from the ICU; however, current literature offers no usable conversion algorithms.

The pain levels of a series of six patients presented here indicate that opioid conversion to lower oral doses does not result in an increase of pain scores. Additionally administered psychotropic drugs may also have an effect on alleviating pain, yet two aspects have to be taken into account: (1) pain aggravation by under-dosing of opioids cannot be compensated by psychotropic medication, and (2) if the opioid dose is titrated to an optimum, psychotropic drugs cannot further reduce this dose. They can only be used to avoid severe side effects of opioid therapy [7]. In the present cases, psychotropic medication was used to treat effects of opioid over-dosing after conventional conversion, and was needed to treat the neuropathic aspects of the respective pain qualities [8].

It is important to note that the conversion to oral opioids is not an "opioid rotation", although one has to calculate an equi- analgetic dose. The concept of opioid rotation addresses the problem of excessive side effects [9] of a single opioid or the insufficient effect on pain [9,10]. This was not the case in the presented patients. In those, we intended to switch an i.v. opioid to an orally applied one, much in the way a morphine drip is switched to oral retarded morphine.

Sufentanil is available as a non-i.v. preparation for sublingual, buccal and nasal administration but not in a long- acting formulation. As the application route switch is usually for a single compound and the long-acting formulation is commercially unavailable, change to long-acting morphine was necessary, but not in the sense of an opioid rotation.

In current references, only the general recommendation to begin oral substitution with approximately 50% of the equivalent dose can be found [10,11]. These recommendations are based on the thought that on one hand the patients have not benefitted from the current opioid and on the other they offer concomitant clinical limitations (i.e. advanced age, renal damage, cardiopulmonary insufficiency, etc.) that makes a 1:1 switch to a new opioid inappropriate.

The patients in the presented cases had an i.v. sufentanil medication near the optimum dose. The available conversion tables and factors suggested a 900% higher dosing than that we eventually applied. Even with a reduction of 50% from the given i.v. dose, the orally administered amount would still have been in excess of 350% of the dose that is finally necessary. This is striking, as inadequately high doses of opioids can lead to severe side effects such as attention deficits, optical hallucinations and ultimately respiratory depression [12,13].

From the present data, we provide evidence that, when converting i.v. sufentanil to oral morphine, a much steeper reduction of the equivalent dose is urgently warranted.

We would like to recommend starting with 10-20% of the calculated equivalent dose of sufentanil infusion when converting to oral long-acting morphine and afterwards adapting the morphine dosage further. Possible co-medication with neuroleptics and benzodiazepines should not be ignored in order to further minimize opioid doses and to decrease severe side effects.

In the possible case that the conversion to a long-acting opioid proves insufficient, a similar approach as usually followed in opioid conversion should be used: In addition to the estimated dose, rescue medication needs to be provided. This can be claimed every hour by the patient and, in the case of using morphine sulfate, doses of 10mg and 20mg with an onset of 15 to 20 minutes should be available. It seems important that none of our patients claimed rescue medication.

Conclusion

Owing to safety considerations, we propose to approach the final opioid dose from a lower dose. By doing this, severe side effects and a possible readmission to the intensive care unit can be avoided. Moreover, since the increased pain perception precedes withdrawal symptoms, correcting the opioid dose in an hourly interval would not have led to withdrawal indicators [14-18].

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