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Expect the Unexpected with Erector Spinae Plane Block in Spine Surgery - Plan for the Worst and Hope for the Best: An Anesthesiologist Perspective-Juniper Publishers

Abstract

Spine surgery is associated with multiple postoperative complications, ranging from simple nausea and vomiting to devastating complications leading to postoperative morbidity or mortality. The postoperative neurological impairment, especially in the neurologically intact patient, is a dreadful event that makes it difficult for the surgeon to perform technically challenging or high-risk spine surgeries. Preoperative or intraoperative factors that can influence the postoperative neurological status include nature and the severity of the pathology, comorbid conditions of the patient, preexisting neurological symptoms, multiple levels involved, complex surgery or instrumentation, surgical blood loss, neurological monitoring, hemodynamic parameters, polypharmacy, and total duration of the surgery.

In addition to several known contributing factors (fixation failure, epidural hematoma, spinal cord edema, and ischemia-reperfusion injury), the role of the erector spinae plane block (ESPB) has recently been cited as a potential cause of postoperative transient paralysis after spine surgery. ESPB is considered a simple and safe regional anesthesia technique that may have an advantage in success rate and analgesic efficacy when used as an adjunct to general anesthesia in spine surgeries. Despite varied patterns of the drug spread, ESPB has been showing promising results due to consistent involvement of dorsal rami that supply all pain generators of the spine surgeries.

The potential role of ESPB in causing postoperative transient neurological complications is a diagnosis of exclusion that requires thorough clinical assessment and step-by-step evaluation using imaging modalities. Before administering ESPB in spine surgery, essential knowledge includes anatomical and technical considerations, drug distribution patterns, safe and effective volumes/types of local anesthetics, and possible associated complications. This review article describes the possible roles of all factors that lead to postoperative neurological impairment and suggests some tips and tricks for using ESPB in spine surgeries to prevent or manage such serious complications appropriately.

Keywords: Transient paraplegia; Erector spinae plane block; ESP block complications; ESP block in spine surgery; Paraplegia due to RA

Keywords: RA: Regional anesthesia; GA: General anesthesia; ESPB: Erector spinae plane block; ERAS: Enhanced recovery after surgery; LA: Local anesthetics; CT: Computed tomography; MRI: Magnetic resonance imaging; ESM: Erector spinae muscles; TP: Transverse process; SMPB: Sacral multifidus plane block; RLB: Retrolaminar block

Introduction

The occurrence of perioperative complications may be inevitable, but their prevention and management are always a shared responsibility of all team members involved. Thorough evaluation of such complications will help develop strategies to prevent and manage the same in the future. A systematic and stepwise approach is warranted before categorizing it as a surgical or anesthetic complication. Several interventions have been introduced in the surgical and anesthetic techniques to improve patient safety and satisfaction. Application of regional anesthesia (RA) alone or as an adjunct to general anesthesia (GA) is one such advance that helps reduce many polypharmacy-related side effects or complications. If a particular complication-reduction modality is inherently causing complications, it requires a comprehensive understanding of the situation and its contributing factors.

An erector spinae plane block (ESPB), a safe and simple RA technique, has shown promising results as an adjunct to multimodal analgesia in various orthopedic, general, thoracic, abdominal, obstetrics, and spine surgeries. In addition to its superior postoperative analgesic profile in spine surgeries at various levels, ESPB reduces hospitalization costs and the possible side effects of extensive anesthetic use. Since opioids have been linked to tumor recurrence [1,2], ESPB also reduces the risk of spine tumor recurrences by significantly reducing its consumption. ESPB meets all criteria suitable for enhanced recovery after surgery (ERAS) protocol [3] by facilitating early discharge and mobilization of patients. Being a novel RA technique, not many complications have been reported so far except for some anecdotal reports of bilateral quadriceps weakness, transient apathy or aphasia, minor neurological complications due to inadvertent intravascular injection of local anesthetics (LA) [4].

Recently, it has been described as a potential cause of transient paralysis after spine surgeries [5]. Therefore, it is essential to understand the differential diagnoses of postoperative neurological impairment, follow the step-by-step approach to rule them out one by one, determine the possible role of ESPB in their development, and learn the tricks for safely administering ESPB during spine surgery. This review article elaborates the essential background knowledge required before and after the administration of ESPB in spine surgeries.

Discussion

Postoperative neurological impairment after spine surgery in a neurologically intact patient is always daunting for the operating surgeon and the patient. Several common theories on neurological deterioration after decompressive spine surgeries include vascular compromise, hypotension, ischemia, direct trauma, or stretching of the neural elements. The major contributing factors of acute paralysis following spine surgery include fixation failure, epidural hematoma, spinal cord edema, and ischemia‑reperfusion injury [6].

Contributory factors

Neurons in the spinal cord are susceptible to ischemia and hypoxia. The mechanisms of spinal cord ischemia are multi-factorial and multi-channel. The pathogenesis of spinal cord lesions after spine surgeries is usually mechanical (pressure) damage via extensive hematoma or edema, resulting in pressure on the spinal cord leading to ischemic damage [7]. An altered cerebrospinal fluid flow dynamic may also cause cord compression [8]. In either case, the ultimate pathogenic cause is a secondary cellular injury due to the disruption of ionic homeostasis, development of free radicals, lipid oxidation, and degeneration of the cytoskeleton [7]. White cord syndrome, an imaging feature of spinal cord ischemia [9], is diagnosed as high intramedullary signal changes on sagittal T2 weighted MRI scans and is often seen in surgeries on the cervical spine.

The spinal infarct is one of the leading causes of paraplegia or quadriplegia in patients with preexisting vascular pathologies (thrombosis) or embolic events during surgery [10]. The anterior spinal cord has a higher risk of ischemia due to fewer anterior spinal artery feeding vessels [10] than the highly vascular posterior spinal cord due to anastomotic pial vessels. The sparing of the posterior column leads to unchanged intraoperative somatosensory evoked potentials [11]. The ischemia-reperfusion injury occurs upon restoring the blood flow to previously ischemic tissues and organs. Increased inflammatory cytokines such as TNF α and IL 1β may be considered vital indicators for evaluating decompression-associated spinal cord ischemia-reperfusion injury [12,13]. Its reported incidence is 2-5.7% following cervical and 14.5% following posterior thoracic decompression surgeries [14, 15].

Transient paralysis is one such complication that manifests itself as a temporary (up to 72 hours) loss of sensations, movements, anal reflexes, and sphincter function below the affected spinal segments [16]. It can occur after vertebroplasty, laminectomy, or thoracic decompressive procedures [17,18]. The longer duration of symptoms, multiple compression sites, and the high degree of preoperative stenosis are considered poor prognostic factors [18].

Who is the culprit?

The exact cause of the postsurgical neurological impairment is a diagnosis of exclusion requiring thorough clinical evaluation and imaging guidance to rule out each contributing factor (Table 1) in a step-by-step manner. Postoperative radiographic studies like computed tomography (CT) scan and magnetic resonance imaging (MRI) can help detect changes suggestive of misplaced implants, hematomas, edema, compressive lesions, white cord syndrome, or direct trauma to the spinal cord. Symptoms due to spinal cord edema typically occur at 48-72 hours post-surgery and may be relieved by anti-edema measures like fluid restriction [19].

The occurrence and severity of ischemia-reperfusion injury correlate with tissue ischemia time, the extent of ischemic tissue, and the oxygen requirement of the affected tissue [20]. The presence of deep tendon and superficial reflexes may rule out the possibility of hysterical paraplegia [18]. After excluding all contributing factors that may cause postoperative neurological impairment, the possible role of ESPB and LA can be considered and further evaluated. It requires an understanding of the anatomical and technical aspects, mechanism of drug spread, factors favoring neuraxial spread, and measures to avoid such incidents in the future [21].

Role of ESPB

ESPB involves depositing the local anesthetic solution between the erector spinae muscles (ESM) and the transverse process (TP) under ultrasound guidance. The ESM consists of three muscles: iliocostalis, longissimus, and spinalis. They arise from and insert into various bony components of the vertebral column [22] and form a paraspinal column that extends from the sacrum to the base of the skull. It gradually tapers upwards in the paravertebral groove on either side of the spinous processes. The retinaculum (thoracolumbar fascia in the lumbar region) that envelops this muscular column also facilitates the LA spread to several thoracic and lumbosacral levels [23]. The diverse multilayered fascial arrangement deep to the ESM may cause the inconsistent LA spread, resulting in multisegmented sensory block mainly involving dorsal rami with sometimes ventral rami.

This Para neuraxial block, when given bilaterally in spine surgery, can be advantageous in success rate and analgesic efficacy [24]. The absence of risks such as hypotension, vascular spread, or pneumothorax makes ESPB relatively safer than epidural anesthesia or paravertebral block. Bilateral ESPB offers effective perioperative analgesia without influencing the hemodynamic parameters. It significantly reduces the perioperative opioid requirements in spine surgeries at various levels (cervical, thoracic, and lumbar, and sacral) [25-32]. Its outcome depends on the volume and concentration of LA used, drug spread, and the anesthesiologist’s experience in selecting and locating the correct level of the TP.

The exact mechanism of action of the ESP block and pattern of the drug spread is still unclear. It has been suggested to anesthetize the spinal nerves by passing through the costotransverse foramen of Cruveilhier, accompanying the dorsal ramus and artery to the paravertebral space [33]. The deposited drug can spread in any direction, such as craniocaudal, anterior-posterior, and lateral-medial planes to reach the paravertebral space, neural foramina, epidural space, or sympathetic chain [34-38]. Fluoroscopic, CT, and MR imaging in living subjects have similarly confirmed the injectate tracking to the paravertebral area, intervertebral foramina, and epidural space following lumbar ESPB [39-42]. There is also a possibility of LA diffusion through the microscopic gaps in the mostly acellular architecture of interlinked collagen fibers of the fascia covering the erector spinae muscle [43].

ESPB at various spine levels

The anatomical differences at the various spine levels can cause varied drug spread and ultimately affect the outcomes of ESPB. Cervical ESPB is technically challenging due to the difficulty in identifying the tips of the cervical transverse processes due to their shorter length. It is mainly given at the C6 or C7 vertebral level. The probe needs to be kept anterolaterally rather than posteriorly to see the cervical TPs [44]. It may not be safe due to its proximity to the neuraxis (shorter transverse processes) and the possibility of bilateral phrenic nerve involvement [45-48].

Thoracic ESPB at the upper vertebral levels (T2 orT3) can be preferred in cervical spine surgery by inserting the needle from caudal-to-cranial direction to achieve the desired LA spread and avoid technical difficulties and complications associated with cervical ESPB. Thoracic ESPB can provide multilevel analgesia even with the small volumes of LA due to rigid boundaries of the thoracic paravertebral spaces that facilitate drug spread at several levels involving ventral and dorsal rami. Lower thoracic level ESPB is mainly performed for lumbar spine surgeries by inserting the needle from cranial-to-caudal direction to achieve the desired LA spread and avoid technical difficulties associated with lumbar ESPB [49,50].

The lumbar ESPB can also be technically challenging due to the increased thickness of the ESMs with their tendinous attachment to the TPs [51, 52] and increased corresponding depth of the intermuscular plane in the lumbar region. The psoas muscle is also closely adherent to the vertebral bodies and the anterior surface of the TPs. The anterior drug spread to include ventral rami may be compromised due to the lack of clear boundaries of lumbar paravertebral spaces [53]. There is a communication through the fat-filled plane between the ESM and TP with the fat-filled psoas compartment containing lumbar nerve roots and plexuses. The spread of LA to the epidural space is possible through this communication [54]. The compressed lamina and the ligaments of the lumbar spine favor LA spread more into the epidural space [55, 56]. Thus, the lumbar ESPB may result in either lumbar plexus block or epidural anesthesia. The resultant weakness in the quadriceps or lower extremity muscles depends on the LA concentration and volume used in ESPB.

Sacral ESPB is mainly described for gender reassignment surgery or perineal surgery [57-61]. Its application for lower lumbar or sacral spine surgery is yet to be determined. The sacral multifidus plane block (SMPB), one of the variants of the paraspinal block, involves the deposition of LA in the plane under the multifidus muscle and bony area between the median and intermediate crests of the sacrum. The possible mechanism of action of SMPB includes blocking the dorsal rami and medial cluneal nerves directly by LA deposition and ventral rami by anterior LA spread through dorsal and ventral sacral foramina. The SMPB may also block the pudendal nerve (S2–S4), lumbosacral plexus, and sciatic nerve via the anterior and cranial LA spread [61, 62].

The role of LA

The possible role of the LA used in ESPB in causing postoperative neurological compromise depends on its inadvertent spread into either the epidural or subarachnoid space. It can be determined based on the occurrence and recovery pattern of the neurological symptoms. Distal-to-proximal and motor-before-sensory recovery patterns are the hallmarks of the differential blockade of the LA [23]. Inadvertent spread of LA into the subarachnoid space can lead to severe hypotension and bradycardia, resulting in unstable intraoperative hemodynamics. The consequences of the epidural spread depend on the density of LA around the spinal nerves, which could be compromised in a subsequent surgical dissection affecting the potentiality of the epidural space.

The concentration of LA, which determines the mass of the drug, also affects the efficacy of any block. The deliberate use of LA in low concentrations can result in a preferred motor-sparing analgesic effect of such high-volume blocks [63, 64]. Bupivacaine and ropivacaine are the most commonly used LAs for bilateral ESPB. Both LA agents consistently display preferential blockade of C-fibres (slow pain) > A-delta fibers (fast pain) > A-beta fibers (touch/pressure) in both preclinical and clinical studies [64-66]. With the increasing concentration, these agents may result in loss of proprioception and loss of motor function. Lipid solubility and higher pKa of LA facilitate intraneural diffusion and ion channel blockade. Ropivacaine exhibits a relative motor-sparing effect due to its lower lipid solubility than bupivacaine [67]. Twenty milliliters of 0.375% ropivacaine is recommended for each side of the bilateral ESPB in adults [68, 69].

Technical aspects of ESPB

Unexpected outcomes like a neurological compromise can be correlated with possible technical errors while administrating ESPB. The first technical aspect is identifying the correct landmark under ultrasound depending on the surgical extent and the desired level of the block. It may further depend on the sonoanatomy quality and the experience of the anesthetist. Sometimes misidentifying the lamina as the tip of the TP can lead to the retrolaminar block (RLB), another variant of the paraspinal block. In RLB, the needle insertion is slightly medial, targeting the lamina of the vertebra instead of the tip of the TP. It works via diffusion of LA into the paravertebral space through the soft tissue gaps between adjacent vertebrae [70]. Both RLB and ESPB were consistently associated with the posterior spread of injectate to the back muscles and fascial layers [37].

Fluoroscopic-guided ESPB can lead to RLB due to the inability to see the tip of TP clearly like under ultrasound, resulting in deposition of the LA solution over the lamina. The proximity of the RLB to the neuraxis can lead to a high probability of epidural spread, which carries the risk of motor weakness. The second important aspect is the ergonomics associated with bilateral ESPB. Administering the bilateral ESPB by standing on only one side of the patient may result in deviation from the ideal needle trajectory on one side compared to the other. Therefore, technical considerations should focus on stabilizing the needle by one person, injecting LA by another person, and performing such bilateral blocks while standing on either side.

The third important aspect includes technical modifications such as keeping an ultrasound probe in a transverse view to help differentiate intramuscular drug spread from the effective linear drug spread between ESM and TP [71]. The fourth aspect is finding alternatives that involve dorsal rami consistently without causing drug spread to other unwanted areas. The thoracolumbar interfacial plane block is one such alternative that targets only the dorsal rami of the spinal nerve. Thus, it can provide more focused dermatomal coverage of the back required for thoracic and lumbar spine surgeries [72, 73]. However, its efficacy in spine surgeries is yet to be determined. We have suggested some tips and tricks for using ESPB in spine surgeries (Table 2), keeping all technical aspects in mind.

Conclusion

Postoperative neurological impairment following spine surgery is a serious concern for the operating surgeon and the patient. The role of ESPB in causing such complications is the diagnosis of exclusion made after a thorough evaluation of clinical symptoms and radiological studies. For that, understanding of various mechanisms involved in ESPB leading to neurological impairment is essential. It should encourage the anesthetists to take extreme precautions while administering this novel block, considering the anatomical differences at various spine levels. Surgeons should anticipate and explain the possibility of neurological deterioration while explaining the risks and benefits of the proposed surgical intervention. Intraoperatively, real-time neurophysiological monitoring is recommended as a useful tool to avoid further neurological deterioration, especially in extensive and multilevel surgeries or in high-risk and neurologically compromised patients.

After identifying or diagnosing such complications, intensive care and regular checking of spinal function are of great importance, along with simultaneous radiological workups to rule out various causative factors. Once paralysis occurs, early diagnosis and early intervention are essential in restoring spinal function. Despite the rare possibility of such complications, ESPB is still a promising option for ensuring effective perioperative analgesia in spine surgeries. It helps reduce postoperative morbidity by keeping the hemodynamic parameters stable and significantly reducing intraoperative blood loss. It can also avoid postoperative complications that lead to delay in mobility and discharge by significantly reducing the need for opioids and polypharmacy. However, further studies are needed to determine the safe concentration and volume of the LA solution used in ESPB, the exact surgery-specific vertebral level to cover desired surgical innervations, and the accurate LA deposition site to prevent spread to undesired areas.

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juniperpublishers-jdvs · 2 years ago

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Veterinary Drug Residue: The Risk, Public Health Significance and its Management

Abstract

Veterinary drugs are any substances applied to or administered to animals for their therapeutic, prophylactic and diagnostic purposes or modification of physiological function or behavior. They are used throughout the world and more than half of all medicines are prescribed, dispensed or sold improperly. In Ethiopia, also different studies revealed the improper utilization of drugs is common. The use of veterinary drugs in food-producing animals has the potential to generate residues in animal derived products and poses a health hazard to the consumer. The most likely reason for drug residues might be due to improper drug usage and failure to keep the withdrawal period. The residual amount ingested is in small amounts and not necessarily toxic. The major public health significances of drug residue are development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, and disruption of intestinal normal flora. The aim of this paper is to review about risk of occurrence of veterinary drug residue, public health effects and management. Even though, veterinary drugs have a great importance in treating, preventing and diagnosing diseases, it has major public health hazards. To avoid this it is important to use these drugs rationally, the safety levels of food must be strictly observed, drug products should be used in accordance with the labeled directions and public awareness should be created on the public health significance of drug residue.

Keywords: Antimicrobial; Drug; Residue; Risk; Veterinary drug

Abbrevations: ABZ: Albendazole; ADI: Acceptable Daily Intake; AMR: Antimicrobial Resistance; APCI: Atmospheric Pressure Chemical Ionization; APEC: Asian-Pacific Economic Cooperation; BZDs: Benzimidazoles; CFR: Code of Federal Regulation; DES: Diethylstilbestrol; DNA: Deoxyribonucleic acid; EC: European Community; EFSA: European Food Safety Authority; ELDU: Extra-label drug use; ELISA: Enzyme linked-immunosorbent assay; ELU: Extra-label use; ESI: Electrospray Ionization; EU: European Union; FAO: Food and Agricultural Organization; FDA: FOOD and Drug Administration; FDACVM: Food and Drug administration Center for Veterinary Medicine; FEB: Febantel; HPLC: High-performance liquid chromatography; IgE: Immunoglobulin E; LC-MS/ MS: Liquid chromatography-mass spectrometry/mass spectrometry; MBZ: Mebendazole; MRL: Maximum Residue Level; NAP: National Academies Press; NOEL: No observed effect level; RNA: Ribonucleic acid; UEMOA: West African Economic and Monetary Union; WHO: World health organization

Introduction

Veterinary drug” means any substance or mixture of substances which is used, or is manufactured, sold or represented as suitable for use, in (1) the diagnosis, treatment, mitigation or prevention of disease or abnormal physical or mental state or the symptoms thereof in an animal; or (2) restoring, correcting or modifying any physical, mental or organic function in an animal [1]. The use of veterinary drugs in livestock production is inevitable as they are essential for treatment of diseases (therapeutic), prevention of diseases (prophylaxis), modification of physiological functions (such as tranquilizers, anesthetic drugs), improvement of growth and productivity (growth promoters) as well as for ensuring food safety [2]. The veterinary drugs are used throughout the world and they comprise a broad variety of classes of chemical compounds including vaccines, antimicrobials, antiparasitics and β-agonists [3]. Antimicrobials are the most important and most frequently used group of veterinary drugs [4]. Antimicrobials are medicine (natural, synthetic or semi-synthetic origin) that inhibits the growth of or destroys microorganisms when applied at low concentrations without causing host damage [5]. Among the antimicrobials that are commonly used in livestock production are tetracyclines, amprolium, penicillin, streptomycin, sulphonamides, tylosin, aminoglycosides, β-lactams, macrolides and lincosamides, quinolones and sulfonamides [6]. While that of antiparasitic agents include anthelmintics or coccidiostats, stilbenes, amphenicols, nitrofurans, nitroimidazoles, carbamates, pyrethroids and sedatives [5].

A residue, defined in the simplest terms, results when a drug or pesticide is deliberately applied to a food-producing animal or plant. Residues of veterinary drugs include the parent compounds and/or their metabolites in any edible portion of the animal product and include residues of associated impurities of the veterinary drug concerned [7]. Residual amounts of antimicrobials or their toxic metabolites found in meat, organs or other products such as milk and egg of food producing animals is called veterinary drug residues [8]. Consumption of such food products poses a major health risk due to the failure of treatment following the development of resistant microorganisms [9]. Many livestock producers treat their animals by themselves. Even if they use the same drugs as veterinarians, they have little understanding of the conditions and quantities to administer or the waiting periods. The uncontrolled use of anti-infectious agents can lead to residues in animal products, especially when users fail to respect waiting periods. The risks of residues in foodstuffs of animal origin could be reflected into several forms [10]. The immediate effect of antimicrobial residue is allergenicity and toxicity in human through the food chain [11]. The long-term health adverse effects such as increased likelihood include disruption of normal human flora in the intestine (microbiological effects), carcinogenicity, and teratogenicity [12]. Other drug residue problems are the development of antibiotic-resistant microbes and drug misuse [13]. The objective of this paper is to review: The risk of occurrence of veterinary drug residue, public health effects and management (Figure 1).

Historical Background

A whole series of known or new foodborne biological and chemical hazards are threatening health [14]. In the European Union (EU), following a string of health crises, the food safety mechanism has evolved towards a risk analysis approach. This shift to the concept of ‘farm to fork’ risk management [15] led to the establishment of food safety agencies at the European level. The risks of residues from veterinary medicinal products used in livestock production were taken on board in the 1980s, most notably through European harmonization of the regulations on medicinal products for veterinary use. Over the past decade, the EU has improved its regulatory framework to better supervise, assess, monitor and control food production under the ‘Food Law’. More recently, the use of anti-infective in livestock and its contribution to the development of antimicrobial resistance has attracted considerable attention [16].

In Africa - particularly West Africa - only microbial pathogens, pesticide residues and aflatoxins have been the subject of measures to protect the safety of food for human consumption. These hazards were perceived as the greatest threat to public health. In April 2007, the eight UEMOA countries (Benin, Burkina- Faso, Cote d’Ivoire, Guinea-Bissau, Mali, Niger, Senegal and Togo) adopted regulation 07/2007/CM/UEMOA concerning plant, animal and food safety in the UEMOA area [17]. More recently, in 2010 and 2011, two training sessions were held in Benin to familiarize these countries with the theoretical framework for health risk analysis [18]. Yet, there have been very few studies on antimicrobial residues affecting food safety [19]. However, in developing countries, failure to respect waiting periods [20] leads to high exposure to antimicrobial residues [21].

Veterinary Drug and their Use in Food Animals

Drug in animals can be used as therapeutic, prophylactic and growth promotion. Therapeutic use refers to the treatment of established infections whereas prophylaxis is the use of drugs either in individual or groups to prevent the development of infections. Growth promoters (GPs) are any antimicrobial agents administered at low or sub therapeutic dose to destroy or inhibits growth of microbe which reduce the yield of food animals. The use of antimicrobials as feed supplements can promote the growth of food animals and also enhance feed efficiency. The uses of GPs are resulting in meat of better quality with less fat and increased protein contests [22]. The use of drugs in food animals is fundamental to animal health and well-being and to the economics of the industry. There are five major classes of drugs used in food animals: (1) topical antiseptics, bactericides, and fungicides used to treat surface skin or hoof infections, cuts, and abrasions; (2) ionophores, which alter rumen microorganisms to provide more favorable and efficient energy substrates from bacterial conversion of feed and to impart some degree of protection against some parasites; (3) steroid anabolic growth promoters (for meat production) and peptide production enhancers (bovine somatotropin for increased milk production in dairy cows); (4) antiparasite drugs; and (5) antibiotics as used to control overt and occult diseases, and to promote growth [23] (Figure 2).

Authorized Veterinary Antimicrobials

The medicinal products containing antimicrobials authorized for veterinary use are those that have passed the marketing authorization process of the competent national authority. After an evaluation of the scientific data proving the efficacy of the product and its safety for humans, animals and the environment the Competent Authority authorizes its importation, distribution and use. No medicinal product may be marketed unless it has first been authorized by the Competent Authority. However, there are huge shortcomings in the implementation because the technical evaluation of a marketing application is limited to an administrative procedure alone especially in most African countries [24].

Prohibited Veterinary Antimicrobials

Prohibited antimicrobials are substances for which it is not possible to determine the Maximum Residue Level (MRL). Chloramphenicol, dimetridazole, ipronidazole, nitroimidazoles, furazolidone, nitrofurazone, and fluoroquinolones are prohibited for extra-label use in food-producing animals [24]. Chloramphenicol is a broad-spectrum antimicrobial against Gram-positive and Gram-negative bacteria. It was not possible to determine an MRL based on the available data. The inability to set a threshold value and shortcomings in the marketing authorization application led to chloramphenicol being classified in 1994 as a prohibited substance for use in food-producing animals. Dapsone, which is used to treat leprosy in humans, is not authorized for use in food-producing animals in Europe because of insufficient toxicology data, making it impossible to determine the acceptable daily intake (ADI) [25]. In the year 1995 European Union (EU) prohibited the use of nitrofurans for the treatment of bacterial diseases in livestock production, due to concerns about the carcinogenicity of their residues in edible tissue [26]. In subsequent years Australia, USA, Philippines, Thailand and Brazil also prohibited the use of nitrofurans in food animals [27] (Table 1).

Origin of Residue

Veterinary drugs are generally used in farm animals for therapeutic and prophylactic purposes and they include a large number of different types of compounds which can be administered in the feed or in the drinking water. The great majority of residues found in edible tissues of animals have their source at the farm of origin. In some cases, the residues may proceed from contaminated animal feedstuffs. By far the most common cause of residues is the failure to observe the proper withholding period following treatment [28].

Risk of Drug Residue for the Public Health

Human health risk can result from the presence of residues of veterinary drugs and/or their metabolites in edible organs and tissues of treated animals, in particular residues in concentrations exceeding the MRL established by Council Regulation 2377/90 [29]. Occurrences of veterinary drug residues pose the broad range of health consequences in the consumers. The residues of antibacterial may present pharmacological, toxicological, microbiological and immunopathological health risks for humans [30].

Anthelmintics, such as benzimidazoles and probenzimidazoles, are veterinary drugs used against endoparasites for the prevention of animal infestations caused by nematodes, cestodes and trematodes in food producing animals. Among the most popular benzimidazoles are Albendazole (ABZ) and Mebendazole (MBZ) [31]. Benzimidazoles (BZDs) such as albendazole (ABZ), fenbendazole and thiabendazole are a kind of broad-spectrum veterinary drugs for prevention and treatment of helminthic parasites in domestic animals. When BZD drugs were fed to domestic animals, they were metabolized and then converted into other compounds in vivo. Thus, these BZDs and their metabolites can be left inedible animal foods or exist in the environment for a period of time. The harmful BZDs and their metabolites residues in some foods lead to a series of toxic effects such as congenic malformations, teratogenicity, diarrhea, pulmonary edemas, polyploidy, and necrotic lymphoadenopathy [32]. Febantel (FEB) is a probenzimidazole with which is further metabolized in vivo to Fenbendazole, a benzimidazole anthelmintic also [31] (Table 2).

Risk Factors for Drug Residue Occurrence

Disease status: The disease status of an animal can affect the pharmacokinetics of drugs administered, which can influence the potential for residues. This can occur either when the disease affects the metabolic system (and consequently drug metabolism), or when the presence of infection and/or inflammation causes the drug to accumulate in affected tissues. For example, cattle with acutely inflamed mastitis quarters, apramycin penetrates these areas of the body, and concentrations of the drug have been observed at ten times over the level recorded from cows without mastitis [33].

Extra-label drug use: Extra-label drug use (ELDU) refers to the use of an approved drug in a manner that is not in accordance with the approved label directions. It occurs when a drug only approved for human use is used in animals, when a drug approved for one species of animal is used in another, when a drug is used to treat a condition for which it was not approved, or the use of drugs at levels in excess of recommended dosages. For instances, the use of enrofloxacin solution as a topical ear medication (Only approved for use as an injection) are the common ELDU in veterinary medicine [34].

Improper Withdrawal Time: Improper withdrawal time is another risk factor; the withdrawal time is the time required for the residue of toxicological concern to reach safe concentration as defined by tolerance. Based on the drug product, dosage form, and route of administration it may vary from few hours to days or weeks. It is the interval from the time an animal is removed from medication until permitted time of slaughter for the production of safe foodstuffs.

Safety Evaluation and Detection Methods of Drug Residues

Safety Evaluation

Acceptable daily intake: Acceptable daily intake (ADI) is the amount of substance that can be ingested daily over a lifetime without appreciable health risk. The evaluation of the safety of residues is based on the determination of the ADI on which in turn maximum residues limits (MRL) is based. The ADI is determined by consecutive estimate of a safe ingestion level by the human population on the lowest no effect level of toxicological safety studies [35]. If the drug is not a carcinogen, the no observed effect level (NOEL) of the most sensitive effect in the most sensitive species divided by a safety factor is used to determine an ADI for drug residues. The FDA will calculate the safe concentration for each edible tissue using the ADI, the weight in kg of an average adult (60 kg), and the amount of the product eaten per day in grams as follows; Safe concentration = [ADI (μg/kg/day) x 60 kg] /[Grams consumed/ day].

Maximum residue level: A tolerance level (or maximum residue levels, MRLs) is the maximum allowable level or concentration of a chemical in feed or food at a specified time of slaughter or harvesting, processing, storage and marketing up to the time of consumption by animal or human [36]. The MRL in various foodstuffs (muscle, liver, kidney, fat, milk and eggs) is determined to minimize the risk of consumer exposure, considering dietary intake. Such considerations as food technology, good farming practices and the use of veterinary medicinal products may also be considered when setting the MRL [37].

Calculating Withdrawal Period: The withdrawal period is determined when the tolerance limit on the residue concentration is at or below the permissible concentration. Withdrawal times are determined in edible, target tissues. Most commonly, they are liver or kidneys as they are primary organs of elimination and typically display a residue for the longest time. During withdrawal studies, the target organ is determined and animals are sampled at various times after drug administration is stopped. For those drugs for which only a kidney or liver tolerances has been established, if a violative residue is found in the target organ, the whole carcass would need to be discarded. On the other hand, for the drugs for which a muscle tolerance has been established, even if a violative residue is found in the kidney or liver a violative residue is not found in the muscle, the carcass would not need to be discarded [38].

Detection Methods

Screening Test: Screening of food products from animal origin for the presence of antimicrobial residues started soon after the introduction of antibacterial therapy in veterinary medicine. Initially it mainly concerned process monitoring in the dairy industry to prevent problems in fermentative dairy production, but from the early 1970s regulatory residue screening in slaughter animals also became more commonly introduced. An efficient screening method needs to be low-cost and high-throughput, able to effectively identify potential noncompliant samples from a large set of negative samples [39].

Advantage of these methods is that they have a wide detection spectrum; they are simple to carry out and cheap; and can be used for the screening of a large number of samples; [40] Possibility of automatization; Reduced time to obtain the result; Good sensitivity and specificity and Detection capability with an error probability (b) < 5% [41]. This method includes a large variety of detection methods, ranging from physico-chemical analysis or immunological detection to microbiological method [42].

Immunological Detection

The immunological methods are based on the interaction of antigen-antibody which is very specific for a particular residue. The most usual technique consists in the enzyme linkedimmunosorbent assay (ELISA) and the detection system is usually based on enzyme-labeled reagents. There are different formats for antigen quantification like the double antibody or sandwich ELISA tests and direct competitive ELISA tests [43]. ELISA kits are allowing the analysis of a large number of samples per kit, do not require sophisticated instrumentation, the results are available in a few hours and are quite specific and sensitive. It has good performance for the analysis of antibiotic residues in meat like tylosin and tetracycline [44], chloramphenicol [45], nitroimidazoles [46] and sulphonamides [47] and also for sedatives [48].

Microbiological Detection

Microbial inhibitions assays are very cost-effective and they have the potential to cover the entire antibiotic spectrum within one test. There are two main test formats: the tube test and the (multi-) plate test. A tube (or vial, or ampoule) test consists of a growth medium inoculated with (spores of) a sensitive test bacterium, supplemented with a pH or redox indicator. At the appropriate temperature, the bacteria start to grow and produce acid, which will cause a color change. The presence of antimicrobial residues will prevent or delay bacterial growth, and thus is indicated by the absence or delay of the color change. This format is commonly applied in routine screening of milk, but it is also increasingly used for analysis of other matrices [49]. A plate test consists of a layer of inoculated nutrient agar, with samples applied on top of the layer, or in wells in the agar. Bacterial growth will turn the agar into an opaque layer, which yields a clear growth-inhibited area around the sample if it contains antimicrobial substances

Biosensors

Different types of biosensors have been developed in recent years as an alternative approach to screen veterinary drugs in meat. In general, these sensors usually contain an antibody as a recognition element that interacts with the analyte. The resulting biochemical signal is measured optically or converted into an electronic signal that is further processed in appropriate equipments [50]. Biosensors can be able to detect simultaneously multiple veterinary drugs residues in a sample at a time [51]. In general, these sensors are valid for control laboratories because they can detect multiple residues in one sample and can thus allow the analysis of a large number of residues and samples [52].

Identification and Confirmation

The next step after initial screening consists in the unambiguous identification and confirmation of the veterinary drug residues in foods of animal origin. The full procedure and the methodologies for confirmatory analysis are costly in time, equipment’s and chemicals. In addition, they require trained personnel with high expertise [53]. Different analytical techniques are available for such purpose. When the target analyte is clearly identified and quantified above the decision limit for a forbidden substance or exceeding the maximum residue limit (MRL) in the case of substances having a MRL, the sample is considered as noncompliant (unfit for human consumption). Identification is easier for a limited number of target analytes and matrices of constant composition [54]. Some examples of the available confirmatory methodologies are as follows: The use of HPLC-electrospray ionization (ESI) tandem mass spectrometry [55] or liquid chromatography-mass spectrometry with atmospheric pressure chemical ionisation (APCI) [56].

ESI technique facilitates the analysis of small to relatively large and hydrophobic to hydrophilic molecules and is thus very adequate for the analysis of veterinary drug residues [57] even though it is more sensible to matrix effects than APCI ionization [58]. ESI and APCI interfaces are the sources of choice to promote the ionization of antibiotics and both complement each other well with regards to polarity and molecular mass of analytes [59].

Public Health Significance of Veterinary Drug Residues

Short Term and Direct Effect

Drugs used in food animals can affect the public health because of their secretion in edible animal tissues in trace amounts usually called residues. For example, oxytetracycline [60] and enrofloxacin residues [61] have been found above the maximum residual level in chicken tissues. Similarly, diclofenac residues were reported to be the cause of vulture population decline in Pakistan [62].

Allergic Reactions: Drug hypersensitivity is defined as an immune mediated response to a drug agent in a sensitized patient, and drug allergy is restricted to a reaction mediated by IgE. An allergic or hypersensitive effect following administration of a drug (i.e., drug allergy is quite similar to that typified by allergic response to protein, carbohydrate, and lipid macromolecules. Allergic reactions to drugs may include anaphylaxis, serum sickness, cutaneous reaction, a delayed hypersensitivity response to drugs appear to be more commonly associated with the antibiotics, especially of penicillin [63]. Certain macrolides may also in exceptional be responsible for liver injuries, caused by a specific allergic response to macrolide modified hepatic cells [64

Long term and Indirect Effect

Mutagenic Effects: The term mutagen is used to describe chemical or physical agents that can cause a mutation in a DNA molecule or damage the genetic component of a cell or organisms. Several chemicals, including alkalizing agents and analogous of DNA bases, have been shown to elicit mutagenic activity [65] that may have adversely affected human fertility [66]. Carcinogenic Effects: The term carcinogenic refers to any substance or an agent capable of altering the genetic makeup of an organism so that they multiply and become rancorous while carcinogen refers to any substance that promotes carcinogenesis, the formation of cancer or having carcinogenic activity. Carcinogenic residues functions by covalently binding intracellular components including DNA, RNA, proteins, glycogen, phospholipids and glutathione [67]. The ban of Diethylstilbestrol (DES), a hormone-like compound used for food producing animals, was as a result its strong carcinogenic effect. Teratogenic Effect: The teratogen applies to chemical agents that produce a toxic effect on embryo or fetus during a critical phase of gestation. Of the anthelmintic, benzimidazole is embryo toxic and teratogenic when given during early stage of pregnancy because of the anthelminthic activity of the drug [67]. Disruption of Normal Intestinal Flora: The normal Intestinal Flora is essential to human health. Not only does the symbiosis exist to contribute to nutrient absorption [68] it also obstructs and inhibits pathogen invasion, as well as aids in the development and optimal functioning of the host immune system [69]. The bacteria that usually live in the intestine act as a barrier to prevent incoming pathogenic bacteria from becoming established and causing disease [70] by producing antimicrobial substances (such as bacteriocins), altering luminal pH, and directly competing against pathogens for nutrients. In addition, commensal bacteria promote angiogenesis and the development of the intestinal epithelium [71]. Antibiotics might reduce total numbers of these bacteria or selectively kill some important species when consumed in food which contain their residues [70]. Development of Antimicrobial Resistance: Indiscriminate use of veterinary drugs, mainly antimicrobials, anthelmintics, and acaricides in food animals also play a major role in the development of antimicrobial resistance (AMR) which has put the public health at risk [72]. This problem is further worsened by irrational use through free access to prescription drugs and their administration at sub-therapeutic concentrations for a long period of time. Such conditions favor the selection and spread of antimicrobial resistant strains in animals, environment and humans [73]. The consequences of antimicrobial resistance in bacteria causing human infections include increased number of infections, frequency of treatment failures and severity of infection, and finally increased costs to society associated with disease. Increased severity of infection includes prolonged duration of illness and increased frequency of bloodstream infections, hospitalization, and mortality [74].

The Extent of Drug Residue in Ethiopia

Globally, more than half of all medicines are prescribed, dispensed or sold improperly. This is more wasteful, expensive and dangerous, both to the health of the individual patient and to the population as a whole that magnifies the problem of misuse of anthelmintic agents [75]. In many African countries, antibiotics may be used indiscriminately for the treatment of bacterial diseases or they may be used as feed additives for domestic animals and birds [76]. The ongoing threat of antibiotic contamination is one of the biggest challenges to public health that is faced by the human population worldwide [77]. Such residues are spreading rapidly, irrespective of geographical, economical, or legal differences between countries.

In Ethiopia, as the study conducted from March 2016 to June 2016 in University of Gondar veterinary clinic revealed, anthelmintic drugs are quite commonly but improperly utilized in the clinic. Three group of anthelmintics namely benzimidazoles (Albendazole, fenbendazole, mebendazole and triclabendazole), imidazothiazole (tetramisole and levamisole) and macrocyclic lactone (Ivermectin) were used. Utilization of limited group of drugs for a long period may favor the development of resistance which is risk factor for drug residues [78]. Though the primary purpose of veterinary drugs is to safeguard the health and welfare of animals [79], 44.3% anthelmintics were prescribed irrationally to treat diseases that were tentatively diagnosed as nonparasitic cases and 92.1% of anthelmintics were utilized to treat diseases that were tentatively diagnosed without getting correct laboratory supported diagnosis. This may be due to inadequate recognition of the disease, unavailability of diagnostic aids for confirmatory tests, and absence of a right drug and to make the treatment broader anthelmintics can be given in combination with other drugs [78].

There also other study conducted in this country in 2007 indicated that the proportion of tetracycline levels in beef; the study focused on the Addis Ababa, Debre Zeit and Nazareth slaughterhouses. Out of the total 384 samples analyzed for tetracycline residue 71.3% had detectable oxytetracycline levels. Among the meat samples collected from the Addis Ababa, Debre Zeit and Nazareth slaughterhouses, 93.8%, 37.5% and 82.1% tested positive for oxytetracycline respectively. Agricultural pesticides are important chemicals that are used to mitigate crop damage or loss and improve productivity. However, pesticides may cause negative environmental and human health effects depending on their specific distribution and use [80]. Its residue has become a major food safety hazard; synergy toxic made it a much higher risk. The toxicity of organic phosphorus, organochlorine, carbamate and other pesticides is mainly manifested as neurotoxicity [81].

Ethiopia is confronted with a number of problems associated with unsafe handling of pesticide distribution and use. Most pesticides used in Ethiopia are imported by international manufacturing companies represented by local agents [82]. Currently, pesticide use practices are changing as a result of the government plan to intensify and diversify agriculture by promoting high value export crops such as flowers and vegetables. For instance, more than 212 types of pesticides with different active ingredients are being used to cultivate roses in Ethiopia. But also, small holders growing vegetables are facing challenges because they are usually resource-poor but also risk averse and under these conditions it is challenging to decide when, how, how much and which pesticide to apply among the hundreds available on the market [80].

Herbicides are widely used in agricultural crops to control weed. Their introduction in the food chain via the environment can be considered a risk for human health due to the toxicity of the most of these compounds. In addition, herbicides are relatively long-lived in the environment, and can be accumulated by means of food chain amplification. Due to their extensive use in cultivation of crops (e.g. soybean, wheat, maize) and relatively stable nature in environments, the residues of herbicides were frequently detected in soil, cereal grain and water. To ensure human food safety, the United State (US), and the European Union (EU) have set maximum residue limits (MRLs) for some herbicide residues in soybean, corn and wheat in the range 0.01-2mg/kg, depending on the particular grain matrix and herbicide, but without the MRL for most herbicides [83].

Use of synthetic acaricides is the primary method of tick control. Synthetic insecticides particularly organophosphates, carbamates, pyrethroids and neonicotinoids have been extensively used by farmers for protecting medicinal and aromatic plants. Consequently, toxic residue of pesticides in raw material posed serious concerns of risk to human health. Therefore, an integrated management including cultural practices, plant-derived products and biological control has been experimented on limited scale [84].

Management of Veterinary Drug Residue

Legislation and Regulations toward Drug Residue

The European Union has strictly regulated the use of veterinary drugs in food animal species. Some of these drugs can be permitted only in specific circumstances (therapeutic purposes) but under strict control and administration by a veterinarian [85]. The use of substances having hormonal or thyreostatic action as well as b-agonists is controlled by official inspection and analytical services following Commission Directive 96/23/EC on measures to monitor certain substances and residues in live animals and animal products. This Directive contributed to a sensible reduction in the number of growths promoting reported cases. However, laboratories in charge of residues control usually face a large number of samples with great varieties of residues to search in short periods of time making it rather difficult. The availability of simple and useful screening techniques is really necessary for an effective control [86].

Establishment of a legislative framework and of an institutional structure is the first step in the assessment and management of drug-related risk. From this point of view, according to pending European legislation the use of veterinary drugs must be based on risk evaluation. The risk due to the use of veterinary drugs is “any risk for animal or public health relating to the quality, safety and efficacy of the veterinary medicinal product and any risk of undesirable effect on the environment”. Risk management is a task of both private and public veterinary services that are involved in the prevention and control of all hazards arising from the use of veterinary drugs. A major tool for veterinarians to prevent and control drug-borne risk is “pharmacovigilance” [87]. Pharmacovigilance is the post-marketing surveillance of veterinary drug and vaccine safety used for prevention, diagnosis and therapy and consists of the report of any adverse effects of a drug by veterinarians, pharmacists, farmers and other health care professionals, in the improvement of knowledge about the pharmacological action of a drug and hence, in the evaluation of the risk/benefit balance of a drug [88].

The main tasks of pharmacovigilance can be summarized as follows: a. Control of clinical safety of veterinary medicinal products; b. Control of potential reaction in man linked to user safety; c. Evaluation of decreased efficacy or lack of expected activity of a veterinary medicinal product; d. Control of maximum residue levels (MRL) of veterinary drugs in food products of animal origin; e. Assessment of risks for the environment related to the use of veterinary drugs; f. Control of the development of drug resistance, with particular concern to antibiotic resistance [89].

Control and Preventive Measures

The control of parasitic helminths in domestic animals relies largely on the use of anthelmintic drugs. But inappropriate and indiscriminate use of anthelmintic leads to the emergence of anthelmintic resistance, treatment failure and increase in mortality and morbidity [90]. Most failures during anthelmintic therapy may occur when the parasite is unknown and anthelmintic drugs are administered empirically. To avoid these problems, it is important to apply confirmatory diagnosis and selection of the right anthelmintic [91]. Maximum Residue Limits (MRLs) in certain products of animal origin, including meat and milk have been established by the European Union. The need for more intensive residue controls becomes stronger considering several studies which indicate that benzimidazoles are not degraded after microwave and oven-baking, storage at -18 ℃ for three to eight months and after cooking. However, no major losses for residues of ABZ, MBZ or FBZ, after roasting of meat and liver (40min at 190 ℃) or shallow frying (muscle 8-12 min, liver 14-19min) in a domestic kitchen [91]. Consequently, conventional cooking hardly protects consumers against the ingestion of residues of anthelmintic veterinary drugs in these foods. Accordingly, the estimation of residues intake through certain food items consumption becomes a necessity to ensure that the Acceptable Daily Intakes (ADIs) of the drugs are not exceeded [92-95].

Irrational use of drugs in veterinary medicine as well as the need for control of their use becomes even bigger problem when used on food producing animals. In this case, there is the possibility that minimal quantities of drugs and their metabolites (residues) which remain in edible tissues or in animal products (meat, milk, eggs, honey) induce certain harmful effects in humans as potential consumers of such food [92]. When drugs are used to improve the productivity of food animals that are intended for human consumption, then there is possibility for producing adverse effects on humans. To prevent this risk, it is necessary to use drugs rationally, i.e., to use them only when they are really indicated, in the right way, at the right time, in the right dose and respecting withdrawal period. The residue control strategy is based on a twostep approach: (1) the detection of residues using sensitive tests with a low rate of false negatives; (2) followed by confirmation, requiring quantification against the MRL and identification with a low rate of false positives. Hence, the residue prevention strategy is based on preventing entry of violative residues in food of animal origin intended for human consumption by proper drug use guide developed for use by both veterinarians and food animal producers include the following: a. Herd health management; Drug residues are best avoided by implementing management practice and herd health program that keep animals healthy and producing efficiently. b. Use of approved drugs. c. Establishment of valid veterinarian-client-patient relationship; the use of prescription drug and the ELU necessitate a veterinary-client patient relationship. d. Proper drug administration and identification of treated animals; before administering or dispensing drugs one has to know the drugs approved for all classes of cattle on the farm and be familiar with approved dosage, route of administration, and withholding time. e. Proper maintenance of treatment records and identification of treated animals. f. Creating awareness of proper drug use, and methods to avoid marketing adulterated products principally educational, total residue avoidance program is based upon the objective of improving the livestock producer’s management and quality control of marketing animals with emphasis on avoidance of drug residues.

Conclusion and Recommendation

Although the veterinary drugs have played a great role in control and prevention of disease in animals and promote the growth of food animals, its use is associated with problems such as development of resistance and residue effects in food animals. These adverse effects are generally due to irrational use of drugs such as misuse, extensive use, failure to keep strict adherence of withdrawal and withholding time of drugs. The development of resistant microorganisms in animals and the presence of drug residue in food of animal origin have significant effect on public health. Globally, more than half of all medicines are prescribed, dispensed or sold improperly. Many livestock producers treat their animals by themselves. The uncontrolled use of anti-infectious agents can lead to residues in animal products. The risks of residues in foodstuffs of animal origin could be reflected into several forms of adverse effects. The great majority of residues found in edible tissues of animals originated in farms but, some cases may proceed from contaminated animal feedstuffs. By far the most common cause of residues is the failure to observe the proper withholding period following treatment. In general, when various types of veterinary drugs; antimicrobials, antiparasitic and β-agonists, food additives, Industrial and agricultural products; pesticide, acaricide, herbicides etc. are used in food producing animals intended for human consumption and in the environment indiscriminately and they pose a great public health effect. Therefore, strict control measures to promote rational veterinary drug use have crucial importance on global economy and public health. Based on above conclusions the following recommendations are forwarded: a. The government should regulate irrational and unauthorized use of drugs and, implement residue control strategy such as management practice and herd health program that keep animals healthy and producing efficiently to avoid drug residues, b. Improperly prescribed, dispensed and sold drug should be regulated, c. Proper maintenance of treatment records and identification of treated animals should be implemented, d. The withdrawal time should be appropriately protected, e. Creating awareness of farmers, consumers and health professionals about drug residues and its public health significance.

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lupine-publishers-scsoaj · 2 years ago

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Gallstone Ileus in the Elderly: Still a Challenge, Report of a Case with Review of the Current Literature

Abstract

Introduction: Gallstone ileus is described as an intestinal obstruction caused by luminal gallstone impaction. It is a mainly geriatric disease with a prevalence of over 25 % in the elderly population. Morbidity and mortality rates are high which are caused due to the delayed presentation, diagnosis and treatment in comorbid patients. Interestingly, since the past century, the optimal surgical procedure in this type of mechanical ileus is still highly controversial and challenging.

Presentation of case: In the current paper we demonstrate our experience with a patient treated at our institution due to gallstone ileus. During surgical exploration the impacted stone in the terminal ileum was removed without preforming a cholecystectomy. This decision was made because of the unstable and septic status of the patient necessitating quick relief of the obstruction and no signs of ongoing severe peritonitis and acute Cholecystitis. She had an uneventful postoperative course.

Discussion & conclusion: While enterolithotomy is performed most commonly because of the low incidence of complications, the risk of developing recurrent biliary symptoms has led to a more aggressive approach with concomitant fistula repair and cholecystectomy.

Keywords: Gallstone ileus, elderly patients, surgical therapy, decision-making

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lupine-publishers-ctgh · 2 years ago

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Lupine Publishers | Case of Application of Syrolimus in a Patient with Progressing Pultifocal Pepatic Nodular Hyperplasia

Abstract

Introduction: A case presented to the public demonstrates the possibility of treatment with Sirolimus in a patient with progressive multifocal liver Focal Nodular Hyperplasia (FNH) with progressive growth and a tendency to formation of liver function insufficiency after splenorenal shunt for portal hypertension.

Material and Methods: Patient E. 08.03.2001 year of birth c Diagnosed with multifocal bilobar nodular liver hyperplasia after splenorenal bypass surgery for portal hypertension, established in 2018/ Sirolimus treatment was prescribed from 06.22.18 to the present.

Conclusion: As a result of the treatment with Sirolimus, a normalization of the level of liver enzymes, bilirubin in the blood is noted. According to radiation methods, a reduction in liver size and FNH size is up to 30%.

Keywords:Multifocal liver Focal Nodular Hyperplasia (FNH); Sirolimus

Introduction

Today, FNH is regarded as a benign vascular formation of the liver. VNG is the second most common benign liver neoplasm [1]. Edmonton first described it in 1958 [2]. FNH most often occurs as a monofocal lesion, in more rare cases there are two or more nodes [3]. FNH is believed to be a hyperplastic response of liver tissue to arterial malformation, and not a true tumor. When conducting radiation diagnostics, the central scar is determined in 44% of cases. The central scar with T2-weighted MRI is hyperintensive [4]. It is possible to determine the filling of blood formation from the center to the periphery, which distinguishes it from monofocal liver hemangiomas. As a rule, in the case of PF, the risk of complications is low; there is no risk of malignancy. Therefore, a patient with VNF rarely requires their surgical removal. The most common indication for removal is pain, which usually occurs with FNH greater than 7 cm in distance [5]. The presence of more than five nodes are characterized as multiple FNH. This is very rare and only a few cases are described in the literature [6]. With progressive multiple FNH, we did not find any treatment recommendations in the literature other than liver transplantation. Therefore, we decided to present a case of treating multiple liver FNHs in a patient using Sirolimus therapy. We also did not find such articles in the literature and therefore we bring this case to the public.

Materials and Methods

Patient E. 08.03.2001 year of birth. Born from the first pregnancy, proceeding against the background of chronic intrauterine hypoxia of the fetus. Childbirth - emergency cesarean section. Height at birth 51 cm, weight 3118 grams, Apgar score of 8 points. In the neonatal period: pneumonia, urinary tract infection, perinatal hypoxic encephalopathy of the fetus, intraventricular hemorrhage. Grew and developed according to age. In August 2008, he suffered bleeding from the dilated veins of the esophagus and stomach. Bleeding is stopped conservatively. The diagnosis of portal hypertension syndrome, cavernous portal vein transformation. In October 2008, surgical treatment was carried out: the formation of spleno-renal anastomosis “side-byside” (Figure 1). No more bleeding was noted. In February 2018, during a control study, multiple FNHs were identified in C1, C4, C8 with dimensions of 87x61 mm, in C7 with dimensions of 51 by 43 mm, 50 by 40 mm (Figure 2). Diagnosed with multifocal bilobar nodular liver hyperplasia after splenorenal bypass surgery for portal hypertension. Blood test for alphafetoprotein 1.66 IU / ml. During the control examination in July 2018, an increase in FNH sizes to 90 by 70 mm, an increase in blood transaminases (Table 1), alkaline phosphatase up to 218.00 IU / L (N 42 - 110), a moderate increase in bilirubin were noted. The patient complained of chronic fatigue, weakness, moderate pain in the liver. lack of appetite.

After examining the child, we came to the conclusion that the observed progression of the disease can lead to the replacement of the liver parenchyma with the subsequent occurrence of organ failure. This could endanger the patient’s life, but there is no possibility of surgery due to the prevalence of the lesion. Sirolimus (Pfizer, USA) from 06.02.2018 was prescribed orally daily at a dose of 3 mg / day until a therapeutic concentration of the drug in blood serum of 6-15 ng / ml was achieved. Due to the excess of the therapeutic interval, the dose of Sirolimus was consistently reduced from 11/06/2018 to 1 mg / day, 02/05/2019 the concentration of Sirolimus was 7.8 ng / ml.

Résultats

As a result of the treatment with Sirolimus, a normalization of the level of liver enzymes, bilirubin in the blood is noted. According to radiation methods, a reduction in liver size and FNH size is up to 30%. Now the patient is feeling well. There is no pain in the liver. Playing sports. Reception of sirolimus continues to date.

Discussion

Multifocal FNH is a rare form of this disease. An even rarer situation arose in our patient, there was a progression of the disease with signs of emerging hepatic cell failure. There was a high risk of severe disease with subsequent liver transplantation. There is an interesting fact that the physiological characteristics of the patient appeared after application of a splenorenal shunt for portal hypertension. Apparently, in the growth stimulation of the nodes, the FNH played the role of impaired portal blood flow. In the available literature, we found only recommendations for liver transplantation in such patients. Teaching ability of Sirolimus to suppress vascular growth through inhibition of M-TOP, we suggested the possible effectiveness of this therapy. After an explanation with the patient and his legal representatives, we started therapy with Sirolimus at a dose of 3 mg / day, then we reduced it to 1 mg / day taking into account the concentration in the blood. The patient had no complications associated with Sirolimus therapy. After a year of treatment, we noted a clear positive trend. The patient’s condition improved, there was no pain, blood counts returned to normal (Table 1).

Conclusion

Of course, this question still requires research in other patients with multiple progressive FNH, in order to draw conclusions about the effectiveness and safety of Sirolimus. But with this patient, we got encouraging results.

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crimsonpublisherssurgery · 2 years ago

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Happy Thanksgiving Day

Warm greetings from Crimson Publishers...! Hope this season is filled with Lots of happiness and joy, wealth, and prosperity. May your home be filled with love on this wonderful occasion of Thanksgiving!

Happy Thanksgiving to you and your family.

#crimsonpublishers #Happy Thanksgiving Day!#open access journal of surgery

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travelingthief · 1 year ago

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Lord Apollo Devotional Post

Divination

Tarot/Oracle decks

Pendulums

Rune stones

Charm casting supplies

Crystal balls

Scrying bowls

All divination tools

Cookie fortunes

Tea leaves

Art

Paint brushes/paints

Canvases

Colored pencils/markers/crayons

Collages

Journals

Art books

Art prints

Anything you made

Sculptures

Zines

Stickers

Any art supplies

Music

Music boxes

Records/CDs/Cassettes

Record players/radios/MP3 etc.

Headphones

Music posters

Band merch

Instruments/String instruments

Dance shoes

Concert tickets

CD book holders

Sun and Light

Sun imagery

Sunscreen

Aloe for sunburns

Golden objects

Matches

Candles

Sunflowers/sunflower seeds

Health and Healing

First aid kits

Medicine

Pain relievers

Band-aids

Ice/heat packs

Rice socks

Masks

Aloe

Ambulance toy cars

Adaptive aids

Archery

Darts

Bow and arrows

Arrow quiver

Dart board

Targets

Bullseye

Myth Related

Snake skins

Snake imagery (Python)

Laurels

Bay leaves (Daphne)

Palm trees (Birth myth)

Ravens/Crows

Crow feathers (Why the crow is black)

Cattle/turtles (Hermes birth myth)

Swans (Pulled His chariot)

Hyacinths (Hyacinthus)

Locks of hair

Food

Vanilla

Honey

Sunny D

Lemons/lemon juice

Oranges/orange juice

Citrus

Water

Devotional Acts

Health

Take your meds

Go to therapy

Exercise

Wear a mask (We are still in a pandemic y’all)

Get vaccinated

Get STI tested

Self care

Learn first aid/CPR

Keep a first aid kit at home/in your car

Learn about alternative medicine

Advocate for accessible healthcare

Advocate for disability rights

Volunteer at a hospital

Give blood/plasma

Volunteer at a retirement home

Learn about anatomy/biology/nutrition

Learn about health conditions/rare disorders

Eat healthy for your body

Help fund surgeries if you can

Trip sit for someone

Listen to your body

Sunlight

Sunbathe

Wear sunscreen

Start a garden

Make sun water

Open all the windows on a sunny day

Music

Go to a concert/show

Listen to music

Make a playlist for someone you love

Make a playlist for Apollo

Learn an instrument/play and instrument

Dance

Sing

Support local bands

Explore new music

Burn CDs

Divination/Prophecy

Daily tarot card/rune stones

Make an oracle deck

Give divination readings

Shadow work

Colormancy

Art

Make something

Draw/paint/craft

Write a poem/story

Color

Make a zine

Go see a play

Get a tattoo

Archery

Throw darts

Use a slingshot

Take up archery

Go to a shooting range

#apollo #apollo offerings #apollo worship #apollon #greek gods #paganism #helpol #hellenic polytheism #theoi #witchblr #hellenic polythiest

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ranahan · 10 months ago

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Free tactical medicine learning resources

If you want to learn first aid, emergency care or tactical medical care for real, you will need to practice these skills. A lot. Regularly. There’s no way to learn them just from books. But if you’re looking to supplement your training, can’t access hands on training, are a layperson doing research for your writing or otherwise just curious, here are some free resources (some may need a free account to access them).

TCCC

The current gold standard in the field is Tactical Combat Casualty Care (TCCC), developed by the US army but used by militaries around the world. There is also a civilian version of the system called Tactical Emergency Casualty Care (TECC). Training materials, Standards of Care, instructional videos, etc. can be accessed at deployedmedicine.com. You’ll need a free account. This should be your first and possibly only stop.

There’s also an app and a podcast if those are more your thing, although I haven’t personally tried them.

More TCCC (video) resources

STOP THE BLEED® Interactive Course

TCCC-MP Guidelines and Curriculum presentations and training videos

EURMED’s Medical Beginner's Resource List has suggested list of video materials (disclaimer: I haven’t watched the playlists, but I have been trained by nearly all of the linked systems/organisations and can vouch for them)

Tactical Medical Solutions training resource page (requires registration; some of the courses are free)

North American Rescue video downloads

Emergency medicine

WHO-ICRC Basic Emergency Care: approach to the acutely ill and injured — an open-access course workbook for basic emergency care with limited resources

Global Health Emergency Medicine — open-access, evidence-based, peer-reviewed emergency medicine modules designed for teachers and learners in low-resource health setting

AFEM Resources — curricula, lecture bank, reviews, etc.

Global Emergency Medicine Academy Resources (links to more resources)

OpenStax Anatomy and Physiology textbook

Open-access anatomy and physiology learning resources

OpenStax Pharmacology for nurses textbook

Principles of Pharmacology – Study Guide

Multiple Casualty Incidents

Management of Multiple Casualty Incidents lecture

Bombings: Injury Patterns and Care blast injuries course (scroll down on the page)

Borden Institute has medical textbooks about biological, chemical and nuclear threats

Psychological first aid: Guide for field workers

Prolonged field care

When the evac isn’t coming anytime soon.

Prolonged Field Care Basics lecture (requires registration)

Aerie 14th Edition Wilderness Medicine Manual (textbook)

Austere Emergency Medical Support (AEMS) Field Guide (textbook)

Prolonged Casualty Care (PCC) Guidelines

Wilderness Medical Society Clinical Practice Guidelines

Austere Medicine Resources: Practice Guidelines — a great resource of WMS, PFC, TCCC, etc. clinical practice guidelines in one place

The Wilderness and Environmental Medicine Journal (you can read past issues without a membership)

Prolonged Field Care Collective: Resources

National Park Services Emergency Medical Services Resources

Guerilla Medicine: An Introduction to the Concepts of Austere Medicine in Asymmetric Conflicts (article)

Mental health & PTSD

National Center for PTSD

Psychological first aid: Guide for field workers

Combat and Operational Behavioral Health (medical textbook)

Resources for doctors and medical students

Or you know, other curious people who aren’t afraid of medical jargon.

Borden Institute Military Medical Textbooks and Resources — suggestions: start with Fundamentals of Military Medicine; mechanism of injury of conventional weapons; these two volumes on medical aspects of operating in extreme environments; psychosocial aspects of military medicine; or Combat Anesthesia

Emergency War Surgery textbook and lectures

Disaster Health Core Curriculum — online course for health professionals

Médecins Sans Frontières Clinical guidelines

Pocket book of hospital care for children: Second edition — guidelines for the management of common childhood illnesses in low resource settings

Grey’s Quick Reference: Basic Protocols in Paediatrics and Internal Medicine For Resource Limited Settings

The Department of Defense Center of Excellence for Trauma: Trauma Care Resources (links to more resources)

#feel free to share and add more #tactical medicine #tactical combat casualty care #prolonged field care #austere medicine #military medicine #tccc #tecc #disaster medicine #wilderness medicine #emergency medicine #emergency medical services #learning resources #writing resources #mandalorian medics #paramedicine #medicine

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biomedres · 29 days ago

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Oral Nutrition Supplements in Enhanced Recovery After Surgery (ERAS): The Pandora’s Box for Prehabilitation Practice

Oral Nutrition Supplements in Enhanced Recovery After Surgery (ERAS): The Pandora’s Box for Prehabilitation Practice in Biomedical Journal of Scientific & Technical Research

Background: Malnutrition is present in 25 to 54% of hospitalized patients upon admission and it has a direct association with increased morbidity, mortality, length of stay (LOS), increased readmissions, and cost of care. The high level of insulin will block the lipolysis and the usage of FAs as the primary fuel (insulin inhibits ketogenesis). Therefore, the body will shift towards gluconeogenesis and use amino acids as the main fuel. This process will lead to protein and skeletal muscle wasting and increase the risk of malnutrition and other postoperative complications. Prehabilitation includes the process of improving the patient’s overall condition before surgery to keep a higher level of the patient’s functional body capacity during surgery and also inhibit postoperative consequences including complications caused by metabolic stress. One of the best practical methods of prehabilitation is the Enhanced Recovery After Surgery (ERAS) protocol. ERAS is a multi professional model to educate patients and improve their physical and nutritional status prior to surgery. The ERAS protocol mainly targets the inflammatory responses and hormonal changes during metabolic stress. This can alter the metabolism leading to suppression of protein-sparing resulting in a decrease in protein wasting. The ERAS program was initially started at CRMC as a pilot quality improvement project in 2017. Furthermore, there is no standardized protocol for ERAS, especially on Oral Nutrition Supplementation (ONS). To date, there is sufficient data to support the benefits of oral nutrition supplementation for patients undergoing metabolic stress. Nonetheless, there is not enough evidence regarding the effectiveness of any specific product over others for improving the patients’ nutritional status prior to surgery and the patients’ overall survival and complications post surgery. Materials and Methods: In this review paper we sought to compare some of the most common nutritional supplements and their ingredients used for ERAS programs in the United States by focusing on the cell signaling effect they may have on metabolism, protein sparing, some elective amino acids, insulin resistance, and glycemic index. Results: The main results revealed that an optimal oral nutrition supplementation should provide an opportunity to trigger the cell signaling pathways that would increase the transcriptional level of endogenous protein synthase while other ingredients would provide further benefits. Conclusion: Despite several review articles and clinical trials and clinical outcome measurements, there is very limited metabolic research on prehabilitation biochemical mechanisms and cell signaling responses pathways. There is an absolute need for mechanistic studies that will help to select the most appropriate formulas.

For more articles in Journals on Biomedical Sciences click here bjstr

Follow on Twitter : https://twitter.com/Biomedres01 Follow on Blogger : https://biomedres01.blogspot.com/ Like Our Pins On : https://www.pinterest.com/biomedres/

#Biomedical Open Access Journals #Open Access Journals on Surgery #Journals on Medical Drug and Therapeutics #journal of biomedical research and reviews #journal of biomedical sciences research review

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nowimjustastranger · 1 month ago

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Hubris | Sneak Peek 1

William looked up from his book when Stan shuffled into the living room with a huge yawn, scrubbing one of his eyes with a fist in a manner that was unfairly endearing. Stan had never been a morning person, Ford fared better in that respect. Even when they were young, Ford was always the one coaxing Stan out of bed in the morning for school, Stan reluctantly following his older brother’s lead as they got ready for the day in tandem.

Stan groaned when he finally noticed William, who was curled up on the sofa, a book about quantum physics left open on his lap. William usually snatched books from Ford’s extensive collection, sometimes even stealing one of his journals to flip through when he was feeling particularly meddlesome, appraising the detailed and organized contents.

��Do you ever sleep?” Stan groused, moving past where William sat to get to the kitchen, pouring himself a freshly brewed cup of coffee. Surprisingly, Stan liked his coffee sweet enough to rot his teeth out of his head with a splash of milk while Ford just drank his black, occasionally adding a bit of milk if he was in the mood to change things up.

Personally, William never saw the appeal of hot bean water.

“You should know by now that I don’t need it.” William mused, his lone eye drifting back down to the book in order to resume reading. He absentmindedly curled his hand in and out of a fist, the robotics beneath his sickly pale skin accommodating the slow curl of his fingers without a hitch.

William still had moments where his body felt foreign to him, unused to having a form that resembled a human. He’d only had this body for thirty years after all. Under the synthetic skin that William maintained using his own power, there was metal, wires, and tubes built to mimic the human structure. Thankfully, the fact that he was essentially a cosmic entity that was harbored in a robot made repairing any damage he sustained rather easy.

“I made breakfast. Bring a plate down to your brother and Fiddleford, they spent all night in the sub-levels again.” William called out, Stan muttering a curse as he raised the mug to take a huge gulp of the steaming surgery concoction.

“What are you guys working on, anyway? I’ve been too busy preparing for Mabel and Dipper’s arrival in two weeks to check in on you three.” William asked as Stan grumpily began to load up a plate of fried eggs, sausage links, and hash browns with ketchup for himself before trudging back into the living room to join William on the sofa. The worn springs squeaked in protest when Stan flopped down, William tucking his bare feet under Stan’s thigh.

“I can barely understand their nerd talk, but I managed to catch something about dimension travel.” Stan grunted between bites of sausage, shoveling the food into his mouth in an utterly barbaric fashion. Stan was lucky that he was a soft-hearted and caring man underneath his gruff exterior, or William would scold him for his appalling behavior more often.

“Dimension travel?” William said blankly, his irritation flaring as he shut the book with a loud snap that made Stan pause, a forkful of egg halfway to his mouth. “I’m assuming he didn’t tell you or Fiddleford that I warned him to keep his grubby paws away from the subject?”

“Nope, he just handed me a blowtorch and handwritten instructions and left me to it.” Stan said with a small shrug, side-eyeing William as he tentatively continued clearing his plate.

“Of course. I should’ve anticipated that he would disregard my concerns.” William scoffed, scrubbing a hand over his face as he unfolded his legs to climb off the sofa, Stan immediately mirroring him with an enthusiasm that William recognized.

“Are you gonna go yell at ‘im?” Stan asked, the expected glimmer of excitement in his blue eyes plain as day as he trailed after William.

“It will undoubtedly devolve into yelling, yes. You Pines boys are stubborn.” William sighed, punching the code into the vending machine panel to access the elevator, Stan leaning against the wall across from him as he polished off the last of his meal.

“It’s one of our less helpful traits, I’ll admit.” Stan said with a tilt of his head, lazily holding his empty plate in his hand, his fork trapped under his thumb.

“It’s not a bad trait, Lee. But, when stubbornness is combined with your brother’s pride, it becomes an issue.” William muttered, dreading the argument that was about to unfold. Everything with Ford was a fight, especially when it came to his research. Once Ford got an idea in his head, it was nearly impossible to talk him out of it.

The elevator came to a stop with a cheery ding, the doors opening to reveal exactly what William had feared. Fiddleford and Ford were assembling a portal. William could do nothing but stare at the towering, triangular structure for several seconds as flashes of his home dimension burning flitted through his mind.

“Yo, Sixer!” Stan yelled in greeting, Ford indulging his brother by turning, lips parted to return the sentiment before his eyes found William. Ford’s grip on the wrench in his hand flexed nervously, jaw snapping shut with a click. Clearly, he knew he was doing something he wasn’t supposed to.

“Disassemble it. Now.” William said firmly, his eye narrowing when Ford’s face pinched.

“I’m afraid I can’t do that, William. Fiddleford and I put too much time and effort into–” Ford began, his posture stiff and awkward.

“I don’t care.” William bit out, cutting Ford off. “You have no idea what you’re messing with.”

#gravity falls #break the mold au #stan pines #ford pines #bill cipher #good bill #stan twins

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symbiosis-online-publishing · 1 year ago

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"Advances in Minimally Invasive Techniques for Spinal Orthopedic and Neurological Surgery"

This special issue of SOJ Surgery explores the latest advancements in minimally invasive techniques for spinal orthopedic and neurological surgery. It includes comprehensive reviews, clinical studies, and case reports that highlight the benefits, outcomes, and challenges associated with minimally invasive procedures in the field of spine surgery. The articles in this issue delve into innovative surgical approaches, cutting-edge technologies, patient outcomes, and the evolving role of robotics and navigation systems in improving surgical precision and patient recovery. Surgeons, researchers, and healthcare professionals will find valuable insights and evidence-based practices for enhancing the quality of care in spinal surgery.

Key points of surgery include:

Surgical Procedures: Surgery encompasses a broad spectrum of procedures, from minimally invasive techniques such as laparoscopy and endoscopy to major surgeries like open-heart surgery and organ transplants. Surgeons may operate on various parts of the body, including the abdomen, chest, brain, musculoskeletal system, and more.

Specialized Surgical Fields: Surgery is divided into numerous specialized fields, including general surgery, orthopedic surgery, cardiovascular surgery, neurosurgery, plastic surgery, pediatric surgery, and many others. Each field focuses on specific anatomical areas or medical conditions.

Preoperative Care: Surgical care begins with a thorough assessment of the patient's medical history, physical examination, and diagnostic tests. Surgeons work closely with an interdisciplinary team to plan and prepare for surgery, ensuring the patient is in the best possible condition for the procedure.

#journal of surgery #surgery journal’s list #journals of general surgery #journal of surgery open access #SOJ Surgery

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clinics-of-surgery · 1 year ago

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Clinics of Surgery (ISSN 2638-1451) Benefits of Journal : Join us for Broad Engagement , Fast track Review Process, Quality Publishing Manuscrits, Easy Accessible.

#Clinics of surgery (ISSN 2638-1451)#Clinics of surgery #Clinics of surgery open access journal .

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ourhaileydavies · 1 year ago

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Skin Closure with Barbed Sutures: An Early Evaluation of Cosmesis and Complications

Author By: Vinay Kumar Tiwari

Abstract

Introduction: Barbed sutures have the potential advantage of decreased operative time and better wound cosmesis due to bidirectional fixation of wound. Present study evaluates the complications and scar cosmesis after skin closure with barbed sutures.

Material and Methods: This was a prospective, observational study. Patients underwent subcuticular skin suturing in surgically created clean wounds. Half of the wound closure was done with barbed absorbable suture and other half with non-barbed absorbable sutures. Comparison of scar cosmesis and wound complications was done.

Results: Mean time taken for suturing per cm of wound was lower in barbed suture group. Suture extrusion rate was higher in barbed suture group. No statistically significant difference was found between cosmesis of scar and rates of infection between the two groups.

Conclusion: The current study did not find any added advantage of using barbed sutures over and above conventional sutures in terms of cosmesis of scar. The only advantage was that of decreased operative time.

Keywords: Barbed sutures; Wound cosmesis; Operative time; Scar; Suture extrusion

Introduction

Barbed sutures have been in use since many decades. They provide effective wound closure due to bidirectional fixation within the wound. The presence of barbs leads to distribution of tension across the wound and also eliminates the need for knots. A barbed suture prevents backward slippage of the sutures, and as a result it does not gape in areas of tension allowing for an aesthetic subcuticular closure. Some clinical studies have shown a better resultant scar.

These sutures allow for a running closure of the wound, with fewer preliminary buried sutures leading to saving of one third to half of the time taken in suturing which can be their greatest benefit [1,2]. This study was done in Indian population where previously no such study has been reported. This study was done by using barbed and non-barbed suture in the same wound by dividing it into two halves thus removing all the confounding factors.

Material and Methods

This prospective, observational study includes 50 patients and was conducted from February 2018 to August 2019. Patients of all age groups were included in the study. The study population consisted of all the patients coming to plastic surgery department at our institute. All patients undergoing primary wound closure in a wound length of greater or equal to 5cm were included in the study. The study included patients with surgically created wounds and included simple surgical incisions and excisional wounds.

Patients with uncontrolled diabetes mellitus, collagen vascular disease, irradiated skin, immunodeficient states, past history of keloid formation, active cutaneous or systemic infection at the time of surgery, chronic renal or hepatic failure were excluded from the study. Preoperatively, patient’s wounds were marked, and dimensions were noted by using Vernier Callipers. Wound was divided into two equal halves and marked. Subcuticular continuous skin closure of one half of the wound was done by conventional polydioxanone sutures while the other half was sutured by barbed polydioxanone sutures. The wound closure was done by the same surgeon. Time taken for surgical closure was noted.

Post operatively various parameters were monitored to evaluate outcome and complications of patients. All patients were followed up for 2 weeks, 1 month, and 3 months after surgery and scar assessment was done by an independent and blinded observer. Scar cosmesis was compared by using POSAS and Vancouver scar scale. Width of the scar, time taken for surgical closure, median scar width and wound infection rates were compared. Wound infection was defined as wound erythema, tenderness or pus discharge from the wound.

Data was entered in Microsoft Excel spreadsheet. Statistical analysis was performed using SPSS (version 18.0). Categorical variables were summarized as frequencies and percentage. Continuous variables were presented as mean and standard deviation or median and inter quartile range based on the normality of data. Normality was assessed using Kolmogorov mirnov test. In case of non-normal or asymmetric distribution, non-parametric test was performed to assess statistical significance.

The following statistical tests were applied

(1) Quantitative variables were compared using Unpaired t-test/Mann-Whitney Test (when the data sets were not normally distributed) between the two groups.

(2) Qualitative variables were compared using Chi-Square test /Fisher’s exact test. A p value of <0.05 was considered to be statistically significant.

Results

A total of 50 patients were studied for a period of 18 months. There were 16 (32 %) women and 34 (68%) men. Maximum (54%) of patients were in the age group of 20-39 years (Table 1). The wounds involved head and neck in 7 patients, trunk in 23 patients, upper extremity in 5 patients, and lower extremity in 25 patients. The width of the scar was evaluated at 2 weeks, one month and 3 months post-operative period. Median scar width (in mm) was compared. Mann-whitney test was performed (Figure 1, 2 and 3).

There was no statistically significant difference in the width of the resultant scars between barbed and non-barbed sutures (Table 2). Time taken in suturing per cm of wound between barbed and nonbarbed suture groups was compared. In our study the time taken for barbed suture was less (23.38 seconds per cm of wound) than conventional absorbable sutures (25.16 seconds per cm of wound) and the difference was statistically significant with a p value of 0.001.

Comparison of Vancouver scar scorewas done at 2 weeks, one month and 2 months’ time period. The median scar score was higher for barbed sutures at one-month postoperative period. Mann-whitney test was performed and the difference was not statistically significant (Table 3). POSAS score (patient) was compared at 2 weeks, one month and 2 months’ time period (Figure 4, 5 and 6). Mann-whitney test was performed and the difference was not statistically significant. The median score was same for both the groups at 2 weeks follow up period. The score was higher for barbed suture group as compared with non-barbed suture group at 1 month and 3 months follow up period. But this difference was not statistically significant (Table 4).

POSAS score (observer) was compared at 2 weeks, one month and 2 months’ time period. The score was higher for barbed suture group as compared with non-barbed suture group at 2 weeks and 1 month follow up period. Mann-Whitney test was performed. The difference was not statistically significant (Table 5). Overall, no significant difference was found in wound cosmesis between barbed and nonbarbed suture group as evaluated by Vancouver scar scale and POSAS observer and patient scar scale. The wounds were evaluated for surgical site complications. Comparison of suture extrusion between groups was done.

In barbed suture group suture extrusion was seen in 9 cases over a period of 3 months. 7 cases were with wounds involving lower extremity and 2 patients with wounds in upper extremity. Only one case of suture extrusion was present in nonbarbed suture group which occurred in upper extremity. Chi square test was performed, p value was <0.01 and the difference was considered as statistically significant. Comparison of surgical site infection at two weeks, one month and 3 months’ time period was done. Chi square test was performed. Higher rate of infection was seen with barbed sutures but the difference was not statistically significant (Table 6).

Discussion

Scarring is an inevitable result of any surgery. Since time immemorial surgeons have been searching for techniques to reduce postoperative starring. Barbed sutures were introduced as tool to reduce scarring. The presence of barbs leads to better tissue fixation and lesser scarring. Theoretically barbed sutures lead to bidirectional fixation of wound which leads to lesser wound gaping and decreased width of resultant scar [1,2]. This was not seen in our study and there was no statistically significant difference in width of the resultant scars between the barbed and non- barbed suture groups.

Decreased width of scar leads to a better aesthetic outcome. A study by Koide et al displayed a significantly better aesthetic outcome in the barbed suture group than nonbarbed suture group [3]. But in our study, there was no statistically significant difference in scar cosmesis as compared by Vancouver scar scale and POSAS (observer and patient scar scale) between the barbed and the non-barbed suture groups. Our findings were similar to studies by Kristen Aliano et al, Amy P Murtha et al, Rubin et al and Grigoryants et al [4-7]. As our study evaluated the scar for only three months, a prolonged follow up is further required to evaluate the scar after remodelling. The time taken per cm of wound was evaluated for both barbed and non-barbed side.

In our study the time taken for barbed suture was less than conventional absorbable sutures and the difference was statistically significant. Similar results were seen in studies done by Koide et al, Kristen Aliano et al,Grigoryants et al, Jeremy P. Warner et al and Blacam et al [3,4,7-9]. Jandali et al, found that using barbed sutures reduced the operative time of unilateral breast reconstruction significantly, but no significant difference was seen in the operative time of bilateral breast reconstruction [10]. The only study showing increased operative time was that by Murtha et al, but the results were not statistically significant [5]. The decreased time taken in barbed suture group in our study is likely because there is no need to put a knot in barbed suture at the ends of the suture line. Also, the handling of suture is improved as the tissue gets fixed with each stitch with a barbed suture.

Our study evaluated the wound for surgical site infection. It was seen that barbed sutures were associated with a higher rate of surgical site infection, but the difference was not statistically significant. Overall, it was seen that the patients having lower extremity wounds had more surgical site infection. This may be due to a greater number of patients having wounds in lower extremity. Also, lower extremity skin is less lax hence wounds are usually closed under more tension leading to wound ischemia and more wound infection. Similar results were seen in studies done by Murtha et al, Jandali et al, where more infections were seen in barbed suture group, but it was not statistically significant [5,10].

Roberto Cortez et al, studied the complications associated with barbed sutures. Their retrospective study found that barbed sutures were associated with significantly higher rates of minor wound complications [11]. The increased incidence of infections in the barbed suture group may be due to the fact that the presence of barbs in the suture leads to colonization of bacteria and resultant higher rates of infection. In our study suture extrusion was seen in 9 out of 50 patients in the barbed suture site as compared to only one patient in the conventional sutures group. The difference was statistically significant. Suture extrusions or stitch abscesses were noted in a total of 10 patients, a probable consequence of the superficial placement of the sutures during subcuticular closure of dermal and subdermal layers.

Similar results were seen in a study done by Rubin et al, which showed increased suture extrusion on the barbed suture side than on the smooth suture side [6]. These findings were consistent with the findings of our study. In a study by Murtha et al, suture extrusion was seen in 10.2 percent of barbed suture subjects as compared with 19.7 percent control suture subjects [5]. The placement of sutures in our study was superficial dermal which might have led to the higher extrusion rate. Further study is warranted to evaluate the extrusion rate of sutures placed in deeper dermis. We used delayed absorbable sutures in our study which could also have contributed the higher rate of extrusion of sutures.

As Grigoryants et al, compared extrusion rate of slow absorbing and rapidly absorbing barbed sutures and found that rapidly absorbing barbed suture had lesser extrusion rate than delayed absorbing barbed sutures [7]. Overall, the complication rate was higher for the barbed suture group. These findings were in contradiction to a study done by Blacam et al, comparing abdominal closure with barbed and non-barbed sutures which found that the complications associated with barbed sutures were lesser. But the follow up period in this study was one month as compared to three months in our study which could have led to the difference in the findings [9].

Conclusion

Barbed sutures lead to decreased operative time but there was no advantage in terms of better scar cosmesis. Though there was an increased rate of surgical site infection barbed sutures, the difference was not statistically significant. The suture extrusion rate with barbed sutures was higher and the difference was statistically significant. Probably study over a larger sample size will give us a better picture. Barbed sutures are costlier than conventional sutures, but their use is less time consuming. So further studies in terms of cost analysis in relation to decreased operative time are warranted to fully evaluate the cost of using these sutures.

#spine surgery #Head and neck surgery #spine #Juniper Publishers #open access journals

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