Pharmacologic Neuromuscular Blockade Research Articles

Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. Retrospective, electronic medical record linkage, cohort study. Quaternary PICU. Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

Enteral feeding tolerance during pharmacologic neuromuscular blockade.

A common misperception is that critically ill patients who receive paralytic therapy will not tolerate enteral nutrition. As a result, some clinicians empirically withhold enteral feedings for critically ill patients who receive neuromuscular blocker pharmacotherapy (NMB). The intent of this review is to examine the evidence regarding enteral feeding tolerance for critically ill patients given NMB. Studies evaluating enteral feeding during paralytic therapy are provided and critiqued. Evidence examining enteral feeding tolerance during NMB is limited. Enteral feeding intolerance is more likely attributable to the underlying illnesses and concurrent opioid analgesia, sedation, and vasopressor therapies. Most critically ill patients can be successfully fed during NMB. Prokinetic pharmacotherapy may be warranted in some patients.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Gastric feeding intolerance in critically ill patients during sustained pharmacologic neuromuscular blockade.

The purpose of this study was to assess gastric feeding intolerance for critically ill patients who received sustained neuromuscular blocker (NMB) pharmacotherapy. Adult patients (>17 years of age) admitted to the trauma intensive care unit who received continuous intravenous NMB pharmacotherapy (rocuronium, cisatracurium, vecuronium, or pancuronium) for ≥48 h during continuous intragastric enteral nutrition (EN) were retrospectively evaluated. Gastric feeding intolerance was defined by initiation of a prokinetic agent (metoclopramide, erythromycin, or both) for an elevated gastric residual volume (GRV) >300 ml and with distention of the abdomen by physical examination, observation of regurgitation or emesis, temporary discontinuation of EN with low intermittent gastric suctioning, or initiation of parenteral nutrition (PN). Patients were evaluated for gastric feeding intolerance for the first 3 days of combined EN and NMB pharmacotherapy. A P value < 0.05 was considered statistically significant. Ten patients of the 47 patients (21%) were intolerant to EN during NMB pharmacotherapy. No statistically or clinically relevant differences in patient characteristics were found between patients who tolerated EN vs those who experienced gastric feeding intolerance, except for a higher median maximum GRV of 125 ml (28, 200) vs 300 (250, 400) ml, respectively (P < 0.001). Five patients responded to prokinetic therapy and five required PN. Most patients tolerated intragastric EN during sustained NMB pharmacotherapy. Presence of NMB pharmacotherapy is not an absolute contraindication for EN.

Optimizing Reversal of Neuromuscular Block in Older Adults: Sugammadex or Neostigmine.

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.

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.

Pupillary Response to Light Is Preserved in the Majority of Patients Undergoing Rapid Sequence Intubation

We determine whether pharmacologic neuromuscular blockade with succinylcholine or rocuronium during emergency rapid sequence intubation affects pupillary response to light. This was a prospective case series of patients undergoing rapid sequence intubation between February 2008 and February 2009. Two blinded, independent emergency physicians assessed pupillary response after administration of neuromuscular blockade and intubation. Cases without pupillary response before rapid sequence intubation were excluded. The primary outcome measure was clinically observable pupillary response. We studied 94 patients undergoing rapid sequence intubation, including 67 (71%) receiving succinylcholine and 27 (31%) receiving rocuronium. Of patients receiving succinylcholine, 61 of 67 (91%; 95% confidence interval 82% to 97%) demonstrated pupillary response after rapid sequence intubation. All patients receiving rocuronium demonstrated preserved pupillary reflexes. κ For interobserver agreement was 0.66. Succinylcholine and rocuronium do not appear to inhibit pupillary response in patients undergoing emergency department rapid sequence intubation.

Feasibility of airway pressure release ventilation in infants with near end stage- neonatal bronchopulmonary dysplasia

Background: Ventilated premature infants with severe, advanced bronchopulmonary dysplasia (BPD) often require high mean airway pressure (MAP) and FiO2 to maintain acceptable gas exchange using conventional mechanical ventilation techniques such as synchronized intermittent mandatory ventilation (SIMV). In addition, they are at risk to develop ep isodes of severe respiratory failure (BPD spells). We report our experience with airway pressure release ventilation (APRV), a ventilation modality which allows spontaneous respiration during a relatively long high pressure phase followed by a shorter release period allowing for CO2 removal from the conducting airways. Despite the higher MAP, the unique APRV flow pattern is thought to decrease volutrauma. Objective: To determine the feasibility and safety of APRV in neonates with severe BPD. Design/methods: Approval for this retrospective review was obtained from Childrens Hospital Los Angeles (CHLA) Institutional Review Board. Patients with advanced BPD treated in the Newborn and Infant Critical Care Unit at CHLA that received APRV at the discretion of the attending neonatologist for develo ping severe respiratory failure between May 2004 and June 2005 were identified and their medical records reviewed. Results: Nine patients were placed on APRV using the AVEA ventilator (CareFusion, San Diego, CA). Eight infants were former extremely premature infants with severe BPD and 1 infant was born at term infant with suspected surfactant protein-B defi ciency. Mean gestational and postmenstrual age was 26.7± 4.9 and 50.5± 9.8 weeks, respectively at the time of initiation of APRV. The duration of APRV was 17.5± 11.9 days. On APRV, patients received higher MAP (29 vs. 15 cm H2O; p < 0.001) and lower FiO2 (0.5 vs. 0.3; p = 0.38) compared to SIMV with pressure support, high-frequency oscillatory ventilation or high-frequency jet ventilation. Seven of the 9 patients had clinical improv ement on APRV within 3 days defined by fewer episodes of severe desaturation, variability in FiO2, and vasopressor/inotrope support. In addition, none of th e infants received pharmacological neuromuscular blockade after the initiation of APRV. Despite the higher MAP, patients did not develop air-leaks and remained hemodynamically stable with normal blood pressure and urine output. Conclusions: These preliminary data indicate that infants with severe BPD tolerate the use of APRV without apparent adverse effects. However, it remains unclear whether APRV is indeed safe and beneficial in former very preterm neonates with seve re BDP and episodes of respiratory failure. Randomized controlled studies are required to determine the safety, efficacy and l ong-term morbidities of this mode of ventilation in neonates.

G.P.2.04 Gene expression and muscle fiber function in a porcine AQM-ICU model

Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation (MV), immobilization (IM) and various pharmacological treatments in intensive care unit (ICU) patients are clinically challenging partly due to the poorly understood intricate cellular and molecular networks and partly due to the unavailability of an animal model mimicking this condition in ICU patients. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization and exposed to various combinations of agents, i.e., pharmacological neuromuscular blockade (NMBA), corticosteroids (CS) and/or sepsis we have analyzed the expression profiles and physiological parameters in the muscle biopsies taken from the m.

A porcine model of acute quadriplegic myopathy: a feasibility study

The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms. Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR). A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation. The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.

Medical Management of Abdominal Compartment Syndrome: Case Report and a Caution

We report the case of a 55 year old woman who developed abdominal compartment syndrome [ACS] following total gastrectomy for caustic ingestion. Contributing factors for the development of ACS included peritonitis and massive fluid resuscitation for cardiovascular support of septic shock. The adverse cardiovascular and pulmonary effects of intra-abdominal hypertension [IAH] were reversed with pharmacological neuromuscular blockade [NMB]. Surgical decompression of ACS was, therefore, postponed, but the patient required re-operation for intra-abdominal sepsis several days later and subsequently died. Although medical management of ACS with NMB may lower IAH and reverse its negative cardiopulmonary effects, surgical decompression may still be required for definitive treatment.

NEUROMUSCULAR COMPLICATIONS OF CRITICAL ILLNESS

BACKGROUND Neuromuscular weakness is common in the setting of critical illness. Over the past two decades, it has been recognized that polyneuropathy or myopathy may develop de novo as a complication of the underlying illness, sepsis, or the medical therapies. This weakness complicates recovery and often contributes to prolonged ventilator dependence. REVIEW SUMMARY The neuromuscular complications of critical illness include critical illness polyneuropathy, an acute myopathy, and prolonged pharmacologic neuromuscular blockade. As a complication of critical illness and the systemic inflammatory response syndrome (usually produced by sepsis), an axonal sensory-motor polyneuropathy may be seen. A myopathy, often called acute quadriplegic myopathy, may develop in a similar setting, often in association with the use of corticosteroids and/or nondepolarizing neuromuscular-blocking agents (NMBAs). Weakness in this latter disorder may result from electrical inexcitability of muscle due to altered membrane sodium channels with reduced sodium currents and loss of myosin thick filament. Some patients, particularly those with abnormal renal or hepatic function, may have prolonged weakness for as long as one week after the use of NMBAs. This large, heterogeneous group of patients are difficult to evaluate due to the limitations imposed by the critical care setting and may have critical illness polyneuropathy, acute quadriplegic myopathy, or both. CONCLUSIONS Neuromuscular weakness may occur in association with a combination of risk factors, including sepsis and multiorgan failure (systemic inflammatory response syndrome), high-dose corticosteroids, and NMBAs. This may take the form of an axonal polyneuropathy, an acute myopathy, or both.

Intraoperative electromyography during thoracolumbar spinal surgery.

Intraoperative electromyography can provide useful information regarding lumbosacral nerve root function during thoracolumbar spinal surgery. Free-running electromyography provides continuous feedback regarding the location and potential for surgical injury to the lumbosacral nerve roots within the operative field. Stimulus-evoked electromyography can confirm that transpedicular instrumentation has been positioned correctly within the bony cortex. However, electromyography has a number of potential limitations, which are discussed in this article along with improved methods to increase the overall efficacy of intraoperative electromyography, including: 1) Electromyography is sensitive to blunt lumbosacral nerve root irritation or injury, but may provide misleading results with "clean" nerve root transection. 2) Electromyography must be recorded from muscles belonging to myotomes appropriate for the nerve roots considered at risk from surgery. 3) Electromyography can be effective only with careful monitoring and titration of pharmacologic neuromuscular junction blockade. 4) When transpedicular instrumentation is stimulated, an exposed nerve root should be stimulated directly as a positive control whenever possible. 5) Pedicle holes and screws should be stimulated with single shocks at low-stimulus intensities when pharmacologic neuromuscular blockade is excessive. 6) Chronically compressed nerve roots that have undergone axonotmesis (wallerian degeneration) have higher thresholds for activation from electrical and mechanical stimulation. 7) Hence, whenever axonotmetic nerve root injury is suspected, the stimulus thresholds for transpedicular holes and screws must be specifically compared with those required for the direct activation of the adjacent nerve root (and not published guideline threshold values).

Succinylcholine-induced Hyperkalemia Following Prolonged Pharmacologic Neuromuscular Blockade

While being treated for the acute respiratory distress syndrome, a 27-year-old woman developed profound hyperkalemia and cardiac arrest following the administration of succinylcholine chloride (SCh). She had none of the risk factors previously described for development of severe hyperkalemia following SCh administrations; however, she had been intermittently treated with nondepolarizing neuromuscular blocking drugs throughout the course of her illness. We suggest that immobilization of critically ill patients with pharmacologic neuromuscular blockade may predispose them to severe hyperkalemia and cardiac arrest following administration of SCh. SCh should be used with great caution in such patients.

The use of pharmacologic neuromuscular blockade as an aid to upper gastrointestinal endoscopy

The use of pharmacologic neuromuscular blockade as an aid to upper gastrointestinal endoscopy