Blocking Drugs Research Articles

Post-operative residual neuromuscular blockade after the administration of a single intubating dose of intermediate-acting non-depolarising neuromuscular blocking agent in adult elective surgical procedures

Objectives: Post-operative residual neuromuscular blockade may result in life-threatening conditions if not properly managed making it a common and significant concern among anaesthesiologists. Among adult elective surgeries requiring single intubating dose of intermediate-acting non-depolarising neuromuscular blocking agent, the study determined the incidence and risk factors associated with post-operative residual neuromuscular blockade during early post-operative period. Materials and Methods: A prospective, open-labelled, non-randomised observational study conducted in an operating room and post-anaesthesia care unit. A total of 175 ASA-PS Class I and II patients admitted in the surgical wards scheduled for elective surgical operation and were administered of a single intubating dose of intravenous intermediate-acting non-depolarising neuromuscular blocking drug. The train-of-four (TOF) method of peripheral nerve stimulation detects the presence of post-operative residual neuromuscular blockade. Results: A significant post-operative residual paralysis was identified in specific age groups (26–35, 46–55 and 56–65), in surgical procedures in the orthopaedic service, and among patients who were given a reversal agent. Residual neuromuscular blockade is still present even if the interval between the last dose of muscle relaxant and the measurement of TOF ratio at the post-anaesthesia care unit was long, however, less than that observed in short interval surgeries. Conclusion: Clinical importance of residual neuromuscular blockade is still evident up to the present time and the present study recommends routine monitoring of neuromuscular blockade and pharmacologic antagonism in the reversal of non-depolarising neuromuscular blocking drugs.

Bioactivity and molecular docking studies of some nickel complexes: New analogues for the treatment of Alzheimer, glaucoma and epileptic diseases

The interaction of the coordination compounds with biological molecules resulted in the investigation of the drug potential of these molecules. In this study, enzyme inhibition of DSA (1–3) coordination compounds that were previously investigated for their anticancer and antibacterial properties was investigated. Also, DSA (1–3) had Ki values of 635.30 + 152.62, 184.01 + 90.05, and 163.03 ± 60.01 µM against human carbonic anhydrase I, 352.23 ± 143.09, 46.2 ± 15.47, and 54.117 ± 18.80 µM against AChE, 310.64 ± 97.35, 35.54 ± 7.01, and 101.51 ± 15.314 µM against BChE, respectively. The biological activity values of these compounds against enzymes whose name are AChE, BChE, and hCAI were compared. Ellman and Verporte methods were used for the study of these enzymes. Cholinesterase inhibitors, also known as anti-cholinesterase and cholinesterase blocking drugs, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. They may be used as drugs for Alzheimer's and myasthenia gravis. It is a common method for comparing biological activity values of nickel complexes with molecular docking calculations. Nickel complexes were studied against enzymes that are human carbonic anhydrase isozyme I for ID 2CAB (hCA I), butyrylcholinesterase for ID 1P0I (BChE), and acetylcholinesterase for ID 1EEA (AChE), respectively.

Impact of Clinical Audit on Adherence to the Guidelines Directed Medical Therapy in Patients Admitted with Heart Failure.

The adoption of guideline recommendations of pharmacotherapy to improve the clinical course of Heart Failure (HF) remains below par. Our objective is to evaluate the impact of clinical audit on adherence to the Guideline-Directed Medical Therapy (GDMT) in patients admitted with acute heart failure with reduced ejection fraction (EF). A prospective interventional study was conducted over a period of 12 months from June 2018 to May 2019 in all patients admitted with acute heart failure with reduced ejection fraction. The discharge prescriptions of patients who met the inclusion criteria were audited for appropriateness in the usage of neurohormonal blockers and Ivabradine, by a clinical pharmacist on a monthly basis. Audit results were presented to the practicing physicians every month and feedback was given. Discharge prescriptions of 716 patients who presented with HF were audited for the reasonable or unreasonable omission of neurohormonal blocking drugs. The first-month audit revealed that the unreasonable omission of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers/ Angiotensin Receptor Neprilisin Inhibitors ( ACEI/ARB/ARNI), Betablockers and Mineralocorticoid Receptor Antagonists (MRA) were 24.5%, 13.1%, and 9.09% respectively, which reduced to nil at the end of the study period (p=0.00). Initiation of Ivabradine before prescribing or achieving the target dose of Betablocker was noted in 38.18% of patients in the first month, which was also reduced to nil (p=0.00) at the end of the study. This study reveals that periodic clinical audit improves adherence to GDMT in patients admitted with heart failure with reduced ejection fraction.

Effects of neuromuscular blocking drugs on viability of human umbilical vein endothelial cells (HUVECs).

ObjectiveThis study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation.MethodsHUVECs were cultivated with 5% CO2 at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10–5, 10–6, and 10–7 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates.ResultsThe neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times.ConclusionsThe findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.

INTUBATING CONDITIONS: PROPOFOL WITH MUSCLE RELAXSANT AND PROFOFOL WITHOUT MUSCLE RELAXANT A STUDY IN TERTIARY CARE CENTRE

Introduction: Neuromuscular blocking drugs, particularly Succinylcholine, may cause serious side effects, but remain in clinical use to facilitate tracheal intubation due to a lack of suitable alternatives. Recent studies have suggested that propofol provides good intubating conditions without muscle relaxants, due to its relaxing action on upper air way.. A search for better and ideal intravenous induction agent has led to propofol, a 2, 6, di-isopropyl phenol which was developed following a series of investigations. Propofol reduces hypertension and tachycardia during intubation. The changes in blood pressure observed are due to both decrease in cardiac output and decrease in systemic vascular resistance. Increasing the depth of anaesthesia by administering supplementary increments of induction agent, opioids or lignocaine may improve conditions. These techniques also protect against the potentially adverse effects of tracheal intubation namely systemic, intra-cranial and intra-ocular hypertensions and tachycardia.
 Material and Methods: The study comprised of 100 adult patients of ASA grade I & II of either sex belonging to the age group of 18-60 years, drawn from various surgical specialties and undergoing surgery under general anaesthesia. Thorough pre anesthetic checkup was carried out in all patients and informed consent for surgery and general anesthesia was obtained. Routine investigations were carried out in all patients. 100 patients were randomly divided into two groups of 50 patients each.
 Results: Youngest patient was of 18 years in group I and 20years in group II. Eldest patient was of 59 years in group I and 60 years in group II. Maximum number of patients were in 20-30 years of age group. The pre induction mean pulse rate (base line) was 101.04±11.78 and 102.36±15.14 in group I and group II respectively. There was slight decrease in pulse rate initially after induction with mean 98.23±13.87 and 97.31±12.60 in group I and group II respectively. The pre induction mean arterial pressure (MAP) (baseline) was 91.47±7.64 and 92.45±9.21in group I and group II respectively. There was slight decrease in arterial pressure initially after induction with mean 80.48±6.29and 83.31±8.41in group I and group II respectively, but the difference was not statistically significant (P>0.05) from the baseline values. There was slight increase in mean arterial pressure just after intubation with mean 93.10±8.47 and 94.58±9.33 in group I and group II respectively, which was not statistically significant (p>0.05).
 Conclusion: In healthy adults, with normal airway, propofol 2.5mg/kg when used alone as inducing agent without the use of any neuromuscular blocking agents produced acceptable intubating conditions, when compared to propofol, 2.5mg/kg along with succinylcholine. It was also demonstrated that there was no significant cardiovascular changes when intubation was done without relaxant after induction with propofol.
 Keywords: Neuromuscular blocking drugs, cardiovascular, propofol

Anaphylaxis in pregnancy: a population‐based multinational European study

Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.

A retrospective observational study of neuromuscular monitoring practice in 30,430 cases from six Danish hospitals

SummaryTimely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train‐of‐four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non‐depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non‐depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non‐depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non‐depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train‐of‐four ratio before tracheal extubation was 0.97 (0.90–1.06 [0.01–2.20]) when non‐depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33–2.70) p < 0.001] and non‐depolarising drugs [2.57 (95%CI 2.32–2.84) p < 0.001] as compared with cases where no neuromuscular blockade drug was used. In conclusion, acceleromyography was almost always used in cases where non‐depolarising neuromuscular blocking drugs were used, but a train‐of‐four ratio of 0.9 was not always achieved. Monitoring was used in less than 30% of cases where succinylcholine was the sole drug used.

Erroneous neuraxial administration of neuromuscular blocking drugs: Clinical and human factors analysis.

Drug errors during neuraxial anaesthesia or analgesia are not well known. To review the clinical consequences associated with incorrect administration of neuromuscular blocking drugs (NMBDs) during spinal or epidural anaesthesia, and to investigate human factors and strategies available to help prevent such errors. A review of reports of neuraxial administration of NMBDs in humans. Published reports of errors involving NMBDs. We searched the period between 1965 and 2019. Error reports in any language. Nonneuraxial drug errors were excluded. We identified 20 reports involving seven different NMBDs inadvertently administered via the epidural or intrathecal routes. All patients developed systemic neuromuscular junction blockade. Fourteen errors occurred while patients were awake. The onset of action was delayed following epidural rocuronium and suxamethonium. The duration of action was prolonged following epidural administration of vecuronium, pancuronium, cisatracrium and suxamethonium. Five patients required emergency airway interventions. Intrethecal gallamine caused convulsions and muscle spasms migrating up the body. Syringe swap was the primary cause for the majority of errors and perceptual errors were the most common. Implementation of recommendations could have prevented the errors. Following the epidural injection of NMBDs the effects are delayed and prolonged. There was no serious morbidity reported following neuraxial administration of the NMBDs used in current practice. Perceptual errors resulting in incorrect syringe choice were the commonest cause. Four measures can be introduced to reduce such errors.

Influência de diferentes anestésicos locais no bloqueio neuromuscular produzido pelo atracúrio em ratos

IntroductionThe association between Local Anesthetics (LAs) and Neuromuscular Blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose‐dependent manner and may potentiate the effects of NMB drugs. ObjectiveThe aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. MethodsMale Wistar rats, weighing from 250 g to 300g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 μg.mL‐1 (Group I); racemic bupivacaine 5 μg.mL‐1 (Group II); atracurium 20 μg.mL‐1 (Group III); atracurium 20 μg.mL‐1 in a preparation previously exposed to lidocaine 20 μg.mL‐1 and racemic bupivacaine 5 μg.mL‐1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane Potentials (MP) and Miniature Endplate Potentials (MEPPs). ResultsLidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. ConclusionsLidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Influence of different local anesthetics on atracurium neuromuscular blockade on rats☆

IntroductionThe association between local anesthetics (LA) and neuromuscular blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. ObjectiveThe aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. MethodsMale Wistar rats, weighing from 250 to 300g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n=5) according to the drug studied: lidocaine 20μg.mL−1 (Group I); racemic bupivacaine 5μg.mL−1 (Group II); atracurium 20μg.mL−1 (Group III); atracurium 20μg.mL−1 in a preparation previously exposed to lidocaine 20μg.mL−1 and racemic bupivacaine 5μg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60minutes after addition of the drugs; 2) Membrane potentials (MP) and miniature endplate potentials (MEPPs). ResultsLidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66±12.48 and 100, respectively, with a significant difference (p=0.003), in comparison to the blockade produced by atracurium alone (55.7±11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. ConclusionsLidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Prevention of Hypertension at Intubation: A Controlled Study of Sublingual Nifedipine

Background: Hypertension and tachycardia-induced after laryngoscopy and intubation can be prevented by various methods like deep inhalation anesthesia, intravenous opioids, topical intravenous lidocaine, intravenous adrenergic blocking drugs, and pretreatment with antihypertensive.Methods: It is a randomized controlled double-blind prospective study of two groups consisting of 30 patients in each group. Group A was the control group and group B were Nifedipine group who were pretreated with Nifedipine. This study aimed to assess the effectiveness of pretreatment with nifedipine in the prevention of the hypertensive response to laryngoscopy and endotracheal intubation in normotensive patients undergoing elective surgery.Result: Sublingual nifedipine was significantly effective in decreasing systolic and diastolic blood pressure produced by laryngoscopy and tracheal intubation, but its role in decreasing pulse rate was not significant. Conclusion: Nifedipine is useful to prevent laryngoscopy and intubation induced hemodynamic response.

Management of Neuromuscular Blockade in the Elderly and Morbidly Obese Patient: What Does the Data Show?

This review addresses considerations for optimal neuromuscular blockade management in the elderly and obese. The evidence for adjusting dosing for common neuromuscular blocking drugs (NMBDs) and their antagonists are discussed. In the elderly patient, aminosteroidal NMBDs have a slower onset and prolonged duration of action. Aging has minimal effects on the organ-independent metabolism of the benzylisoquinolinium NMBDs. Slower circulatory times and reduced renal function in the elderly also have implications on the clinical effects of NMBD antagonists. Since drug clearance and distribution is not the same in obese and in lean patients, dosing based on the total body weight (TWB) will result in excess NMBD administration. Various dosing scalars such as ideal body weight (IBW), lean body weight (LBW), and fat-free mass (FFM) have been proposed but each has its own limitations. NMBDs should be dosed based on ideal body weight in obese patients. Optimal sugammadex dosing in obese patients remains controversial while neostigmine administration should not exceed 5 mg. Elderly and obese patients have an increased risk of developing complications in the perioperative period, particularly when NMBDs are administered. Vigilance, careful titration, and quantitative monitoring are warranted to care for these challenging patients.

Spontaneous recovery of neuromuscular blockade is an independent risk factor for postoperative pulmonary complications after abdominal surgery: A secondary analysis.

In intermediate-to-high-risk patients, major abdominal surgery is associated with a high incidence of postoperative complications, mainly pulmonary. Neuromuscular blocking drugs have been suggested as a contributing factor, but this remains unproven. To define the relationship of neuromuscular blockade management (reversal) with postoperative pulmonary complications (PPCs). The individualised PeRioperative Open-lung approach Versus standard protectivE ventilation in abdominal surgery study was a prospective, multicentre, four-arm, randomised controlled trial. This is a secondary analysis of the data. Twenty-one teaching hospitals in Spain. The study was conducted between 2 January 2015, and 18 May 2016. Age more than 18 years with an intermediate-to-high risk for PPCs, scheduled for major abdominal surgery lasting more than 2 h. Exclusion criteria included pregnancy or breastfeeding, and moderate-to-severe organ diseases. The mode of reversal of neuromuscular blockade determined two patient groups: pharmacological reversal versus spontaneous recovery. The primary outcome was a composite of PPCs during the first 30 postoperative days. The association between categorical variables and PPCs within 30 days was studied. Univariate and multivariable logistic regression modelling and propensity score analyses were performed. From the 923 patients included, 596 (64.6%) presented with PPCs within 30 days after surgery. Patients who developed these complications were older with a higher BMI, a lower pre-operative SpO2, a higher ASA physical status score and a higher incidence of arterial hypertension, diabetes mellitus or chronic obstructive pulmonary disease. Pharmacological neuromuscular blockade reversal was associated with a lower incidence of PPCs (odds ratio 0.62, 95% CI 0.47 to 0.82). Spontaneous recovery of neuromuscular blockade was an independent risk factor for PPCs in patients with intermediate-to-high risk, undergoing abdominal surgery. We suggest this factor should be included in future studies on PPCs. clinicaltrials.gov identifier: NCT02158923.

Current state of the roles of alcohol septal ablation and surgical myectomy in the treatment of hypertrophic obstructive cardiomyopathy.

Hypertrophic cardiomyopathy is a genetically determined disorder resulting in left ventricular hypertrophy. In a majority of the estimated 20 million people affected worldwide, left ventricular outflow obstruction is present at rest or with provocation. The presence and degree of obstruction influence the symptomatic presentation, treatment strategies and prognosis of affected individuals. Pharmacologic therapy with beta-adrenergic blocking drugs and calcium channel blockers is the principal treatment strategy in symptomatic patients with left ventricular outflow obstruction but is ineffective in many patients. When symptoms of exertional shortness of breath, chest pain and/or syncope prove refractory to medical therapy and there is persisting left ventricular outflow obstruction, or when there is drug intolerance, septal reduction strategies (surgical myectomy and alcohol septal ablation) are quite effective. Selection of the optimal septal reduction strategy for a given patient has become controversial and is determined largely by the medical system providing treatment strategies for the patient. Regretably, there are no randomized trials comparing myectomy and ablation and none are anticipated. The comprehensive Hypertrophic Cardiomyopathy Guideline Statements published in 2011 and 2014 differ significantly with the earlier statement favoring surgical myectomy and the more recent statement giving equal class I status to the two septal reduction strategies in adult patients with drug-refractory symptoms. Recently published studies of long-term follow-up of patients after alcohol septal ablation in Europe, where surgical myectomy is rarely performed, confirm long-term safety and effectiveness with survival free of cardiac events exceeding 96% at 15 years. The lesser degree of discomfort and more rapid recovery associated with the minimally invasive catheter-based alcohol ablation procedure coupled with the recently published long-term safety data favor an increased use of this strategy in symptomatic adult patients with hypertrophic obstructive cardiomyopathy (HOCM).

The role of anaesthesiologists in lethal injection: a call to action.

In 2006, Michael Angelo Morales, a California death-row inmate, was scheduled to be executed by lethal injection. 1 Gawande A When law and ethics collide–why physicians participate in executions. N Engl J Med. 2006; 354: 1221-1229 Crossref PubMed Scopus (68) Google Scholar Morales challenged the state's lethal injection protocol in court, arguing that administration of pharmaceutical drugs without oversight by personnel with medical expertise or training would violate his Eighth Amendment rights. 2 Michael Angelo Morales v Roderick Q Hickman. Number C 06 219 JF. District Court, Northern District of California, CA, USA. Feb 14, 2006. Google Scholar The basis of his claim was that the protocol created foreseeable and undue risk of excessive pain, given the potential for consciousness during drug administration. 2 Michael Angelo Morales v Roderick Q Hickman. Number C 06 219 JF. District Court, Northern District of California, CA, USA. Feb 14, 2006. Google Scholar The California protocol called for an injection of a three-drug cocktail: thiopental, a barbiturate intended to render the inmate unconscious; pancuronium, a neuromuscular blocking drug that induces paralysis and causes cessation of breathing; and potassium chloride, to induce cardiac arrest. 3 Schwarzenegger A Tilton JE State of California lethal injection protocol review. https://files.deathpenaltyinfo.org/legacy/files/pdf/CALethInject.pdfDate accessed: August 6, 2019 Google Scholar Morales argued that the potential for consciousness during the administration of pancuronium and potassium chloride constituted cruel and unusual punishment. 2 Michael Angelo Morales v Roderick Q Hickman. Number C 06 219 JF. District Court, Northern District of California, CA, USA. Feb 14, 2006. Google Scholar

Normal and difficult airways in children: "What's New"-Current evidence.

Pediatric difficult airway is one of the most challenging clinical situations. We will review new concepts and evidence in pediatric normal and difficult airway management in the operating room, intensive care unit, Emergency Department, and neonatal intensive care unit. Expert review of the recent literature. Cognitive factors, teamwork, and communication play a major role in managing pediatric difficult airway. Earlier studies evaluated videolaryngoscopes in a monolithic way yielding inconclusive results regarding their effectiveness. There are, however, substantial differences among videolaryngoscopes particularly angulated vs. nonangulated blades which have different learning and use characteristics. Each airway device has strengths and weaknesses, and combining these devices to leverage both strengths will likely yield success. In the pediatric intensive care unit, emergency department and neonatal intensive care units, adverse tracheal intubation-associated events and hypoxemia are commonly reported. Specific patient, clinician, and practice factors are associated with these occurrences. In both the operating roomand other clinical areas, use of passive oxygenation will provide additional laryngoscopy time. The use of neuromuscular blockade was thought to be contraindicated in difficult airway patients. Newer evidence from observational studies showed that controlled ventilation with or without neuromuscular blockade is associated with fewer adverse events in the operating room. Similarly, a multicenter neonatal intensive care unitstudy showed fewer adverse events in infants who received neuromuscular blockade. Neuromuscular blockade should be avoided in patients with mucopolysaccharidosis, head and neck radiation, airway masses, and external airway compression for anticipated worsening airway collapse with neuromuscular blocker administration. Clinicians caring for children with difficult airways should consider new cognitive paradigms and concepts, leverage the strengths of multiple devices, and consider the role of alternate anesthetic approaches such as controlled ventilation and use of neuromuscular blocking drugs in select situations. Anesthesiologists can partner with intensive care and emergency departmentand neonatology clinicians to improve the safety of airway management in all clinical settings.

Evolutionary medical insights into the SARS-CoV-2 pandemic.

The author apply concepts and tools from evolutionary medicine to understanding the SARS-CoV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven by three main factors: (i) bat immune systems that rely on low inflammation but high efficacy of interferon-based defenses; (ii) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and pre-symptomatic transmission; and (ii) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for COVID-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the phenome-wide association study also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality. Lay Summary: SARS-CoV-2 is a bat virus that jumped into humans. The virus is adapted to bat immune systems, where it evolved to suppress the immune defenses (interferons) that mammals use to tell that they are infected. In humans, the virus can apparently spread effectively in the body with a delay in the production of symptoms and the initiation of immune responses. This delay may then promote overactive immune responses, when the virus is detected, that damage the body as a side effect. Older people are more vulnerable to the virus because they are less adapted to novel infectious agents, and invest less in immune defense, compared to younger people. Genes that increase risk of mortality from SARS-CoV-2 are functionally associated with a drug called amlodipine, which may represent a useful treatment.

Pseudocholinesterase Deficiency Considerations: A Case Study.

Pseudocholinesterase deficiency, sometimes called butyrylcholinesterase deficiency, is a rare disorder in which the neuromuscular blocking drugs succinylcholine and mivacurium cannot be metabolized properly in the blood plasma. This disorder can either be acquired as a result of certain comorbidities or it can be inherited genetically. Anesthesia providers must understand the pathophysiology of pseudocholinesterase deficiency and be prepared to safely and effectively manage patients who show signs and symptoms consistent with the disorder after the use of the indicated neuromuscular blocking drugs. This article summarizes the pharmacologic and physiologic data relevant to understanding the basic pathophysiology associated with pseudocholinesterase deficiency and illustrates a case study of a young woman suspected of having the disorder after a prolonged delay in emergence from general anesthesia.

Angiotensin Receptor-Neprilysin Inhibition (ARNI) in Heart Failure.

Recognition that neurohormonal activation plays a central role in the pathogenesis of heart failure (HF) led to the development of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers, mineralocorticoid receptor antagonists and beta blockers. While there has been substantial success with these neurohormonal blocking drugs in patients with HF with reduced ejection fraction (HFrEF), persistently high rates of morbidity and mortality in this population underscore the need for more effective therapies. As part of the systemic neurohormonal activation that takes place in patients with HF, systems that counteract the adverse effect of the renin angiotensin aldosterone system (RAAS) and sympathetic nervous system (SNS) are also activated. Evidence that neprilysin metabolizes many of the effector molecules produced by these counter-regulatory systems raised the possibility that inhibition of this enzyme might be beneficial. However, since angiotensin II is a substrate of neprilysin, inhibition of the enzyme alone would increase levels of this peptide. Thus, treatment strategies that combine RAAS blockade with neprilysin inhibition were sought. Recent large scale randomized clinical trials (RCTs) have provided compelling evidence that sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is superior to an ACEI in reducing mortality and HF hospitalization and in improving quality of life in patients with stage C HFrEF. In these trials, sacubitril-valsartan was found to be safe and well tolerated. This review presents the rationale for using ARNIs, describes the RCTs showing their efficacy, summarizes updated recommendations from recent guidelines, and provides practical points about ARNI initiation and up-titration.

A Comparative Study of Atracurium and Cisatracurium in paediatric cleft Lip and Cleft palate surgeries

General anaesthesia with intubation with RAE tube is preferred in children undergoing cleft lip and palate surgeries. Neuromuscular blocking drugs (NMBDs), are given to infants and children to attain ideal intubating conditions by providing adequate muscle relaxation. In contrast to routinely used atracurium, cisatracurium is comparatively a newer drug with lesser histamine release. The study was designed with the aim to compare the efficacy of atracurium (2×ED95) and cisatracurium (4×ED95).90 patients, 6 months-5 years, ASA class I &II were randomly allocated to cisatracurium and atracurium group. After administration of induction agent, dose of neuromuscular blocking drug atracurium 0.5mg/kg or cisatracurium 0.2mg/kg was given to the patients. The intubating conditions were graded using ‘Cooper et al’ scoring system. Neuromuscular blockade was assesed using train of four ratio. Alongwith intubating conditions, onset and duration of action, hemodynamic effects, and signs of histamine release were measured in both the groups. In the atracurium group the mean score according to ‘Cooper et al'scale was 6.86±0.54, whereas in the cisatracurium group it was 8.12±0.64, the difference between the groups was statistically significant. Time of onset was found to be 2.7±0.12 minutes in the cisatracurium group and 3.28±0.64 minutes in the atracurium group. Duration of action was 64.6±6.18minutes in the cisatracurium group as compared to 35.4±4.64minutes in the atracurium group. Cisatracurium(0.2mg/kg) is more efficacious as compared to atracurium(0.5mg/kg)with respect to intubating conditions, it has a faster onset of action, good intraoperative hemodynamic parameters, longer duration of action with no side effects.