Doses Of Neuromuscular Blocking Agents Research Articles

Sugammadex introduction is associated with increased dosing of neuromuscular blocking drugs

BackgroundThe introduction of sugammadex, a relatively new medication that can quickly and effectively reverse deeper states of neuromuscular blockade, may cause anesthesiology clinicians to change dosing patterns of neuromuscular blocking agents. MethodsWe retrospectively examined intraoperative aminosteroid neuromuscular blocking agent (NMBA) usage at a large tertiary care hospital from 15 months before until 39 months after the introduction of sugammadex. For each surgical case using commonly used aminosteroid NMBAs, we normalized the observed dose to a predicted dose of NMBA calculated using case duration and patient weight. An observed-to-predicted aminosteroid NMBA dose ratio was calculated for all surgical cases in the QI project and this metric was used to compare NMBA dosage in the pre-sugammadex epoch with that in the post-sugammadex epoch. ResultsThe observed-to-predicted dose ratio increased from 0.509 ± 0.007 (n = 25,132) in the pre-sugammadex epoch to 0.524 ± 0.007 (n = 51,801) in the post-sugammadex epoch (p= 0.007). Using segmented regression with co-variate analysis, the regression slope representing daily change in aminosteroid NMBA observed-to-predicted dosage ratio increased from -1.06×10−4± 4.4 × 10−5 (n= 24,779) in the pre-sugammadex epoch to 9.01×10−5± 1.8 × 10−5 in the post-sugammadex epoch (n= 51,218) (p < 0.001). ConclusionAminosteroid NMBA dosage increased after the introduction of sugammadex. Potential explanations for this increased dosage include risk compensation, which is the tendency to engage in higher risk activities after a new safety measure is available.

Vigilance: the behavioral impact of quantitative monitoring on administration and antagonism of neuromuscular blocking agents.

The aim of this study was to determine whether use of acceleromyography (1) changes dosing of neuromuscular blocking agents (NMBAs), and (2) increases the time between neostigmine administration and extubation, when compared with subjective assessment of neuromuscular blockade. For this retrospective study, data were collected from patient electronic medical records. Patients were included if they had received an NMBA as part of a general anesthetic in 2013 and 2014. Data were analyzed by category of monitoring device: quantitative monitor (acceleromyograph [AMG]) or subjective device (peripheral nerve stimulator [PNS]). Outcomes measured were the total dose of NMBA administered and, the timing of the last dose of NMBA and anticholinesterase relative to tracheal extubation. Results from multivariate models showed that use of acceleromyography was not associated with a change in the total dose of NMBA administered. In contrast, the number of times any monitor was used, as determined by the frequency with which the train-of-four count (TOFC) was recorded, correlated with the administration of greater amounts of rocuronium (P < 0.01) and vecuronium (P < 0.01). The use of acceleromyography did not prolong the time interval between neostigmine administration and tracheal extubation. The number of times any monitor was used during an anesthetic was associated with a decrease in this time interval. The interval decreased an average of 2.7min each successive time the TOFC was recorded (P < 0.01). The data presented provides insight about the behavioral engineering inherent to the practice of anesthesiology. Introduction of neuromuscular blockade assessment appeared to increase provider vigilance in dosing of NMBAs-regardless of assessment method. The frequency of intraoperative monitoring (quantitative or subjective) was associated with an increased total dose of NMBA administered and decreased time interval between the last dose of neostigmine and extubation.

Neuromuscular Blocking Agent Use in Acute Respiratory Distress Syndrome: Which Variable is Important?

Background: The study of neuromuscular blocking agents (NMBAs) in the management of acute respiratory distress syndrome (ARDS) has provided conflicting results in terms of their effect on mortality. Objectives: The main purpose of this study was to evaluate mortality in ARDS patients who underwent NMBA. Methods: A retrospective secondary analysis of 4200 patients with ARDS was collected from two academic medical centers, Tehran, Iran. This study was performed to assess the impact of NMBAs use in ARDS patients with different subgroups including mild and moderate-to-severe ARDS, age more and less than 65 years, having medical turnover vs. not-having, and high acute nursing care vs. moderate to low nursing care. Results: Intensive care unit (ICU) mortality has occurred in 1169 (27.8%) participants. The mortality rate was 28.6% and 27.5% in patients with mild and moderate-to-severe ARDS, respectively. In the subjects without medical turnover, the moderate dose of NMBAs significantly reduces the mortality of patients (P=0.044). In patients who need high acute nursing care, increasing the NMBAs dose significantly reduces patients’ mortality (P=0.010). In addition, increasing the NMBAs doses significantly reduces ICU length of stay (LOS). Conclusion: This study provides evidence that the administration of different doses of NMBAs had no effect on patients’ mortality with mild or moderate-to-severe ARDS. However, higher doses of NMBAs than low doses increased the risk of mortality in patients over 80 years and can reduce the risk of death in patients less than 55 years.

Survey of neuromuscular monitoring and assessment of postoperative residual neuromuscular block in a postoperative anaesthetic care unit.

The use of neuromuscular blocking agents (NMBAs) is common during general anaesthesia. Neuromuscular monitoring with a peripheral nerve stimulator (PNS) is essential to prevent postoperative residual neuromuscular block (PRNB), defined as a train-of-four (TOF) ratio < 0.9. PRNB remains a common complication and may contribute to morbidity in the postoperative anaesthetic care unit (PACU). An online survey was sent to anaesthesiologists in our department to assess their knowledge and clinical practices related to neuromuscular blockade. Next, a study was conducted on adult patients scheduled for elective surgery under general anaesthesia requiring NMBAs. Upon admission to the PACU, TOF monitoring was performed. A large proportion of anaesthesiologists showed a lack of knowledge of neuromuscular blockade or non-adherence to the best clinical practices associated with it. The majority (98.7%) stated that they did not routinely use PNS monitoring. In the clinical study, TOF monitoring was only used in 17.9% of the 335 patients who were assessed. The prevalence of PRNB was 33.4% and was associated with the elderly (age ≥ 65 years), a higher dose of NMBA used, a shorter duration of surgery, and a shorter duration between the last dose of NMBA and measurement of PRNB in the PACU. The incidence of adverse symptoms in the PACU was observed to be higher in patients with PRNB. PRNB remains a clinically significant problem, but routine PNS monitoring is rare in our institution. This is compounded by inadequate knowledge and poor adherence to best clinical guidelines related to neuromuscular blockade.

Association Between Intermediate-Acting Neuromuscular-Blocking Agents and Short-Term Postoperative Outcomes in Patients with Gastric Cancer.

PurposeThis study examined whether different neuromuscular-blocking agents (NMBAs) work differently on the short-term outcomes of gastric cancer patients in terms of laboratory test results and severity of postoperative illness, and whether the effect is dose-related.Patients and MethodsData of 1643 adult patients receiving gastric cancer surgery were analyzed by employing generalized linear models (GLMs), to explore the effects of different NMBAs on neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR) at postoperative day 1 (POD1), POD3, POD7, and return to intended oncologic therapy (RIOT), among others. We adjusted multiple covariants, including patient-, anesthesia-, and surgical complexity-related risk factors.ResultsWithout adjusting dosage of NMBAs, POD1NLR, POD1PLR (P < 0.05), POD3NLR, POD7NLR, POD3 lymphocytes, POD7LMR (P < 0.01) in gastric cancer patients administered with benzylisoquinoline NMBAs worsened, and the administration of aminosteroidal NMBAs was associated with less risk of transfer to ICU (P < 0.01); without adjusting the types of NMBAs, the highest dose of NMBAs postponed the RIOT (P < 0.05) and was negatively associated with POD3NLR, POD7NLR and POD7LMR (P < 0.01), and increased risk of postoperative transfer to ICU (P < 0.01). When patients given benzylisoquinolines were re-divided in terms of five equal quintiles, from low to high dose, RIOT was delayed and POD7LMR decreased significantly in the fourth and fifth quintile groups as compared to the first quintile group. A higher risk for postoperative transfer to ICU was found in the fifth quintile group as compared to the first quintile group.ConclusionPatients with gastric cancer given benzylisoquinoline NMBAs had more unfavorable short-term outcomes, such as more severe inflammation and increased risk of transfer to ICU than their counterparts administered aminosteroidal NMBAs, and the effect of benzylisoquinolines was dose-related. The effect of aminosteroids on short-term outcomes was not dose-related in the dosage range we used.

Dose-dependent Association between Intermediate-acting Neuromuscular-blocking Agents and Postoperative Respiratory Complications.

Duration of action increases with repeated administration of neuromuscular-blocking agents, and intraoperative use of high doses of neuromuscular-blocking agent may affect respiratory safety. In a hospital-based registry study on 48,499 patients who received intermediate-acting neuromuscular-blocking agents, the authors tested the primary hypothesis that neuromuscular-blocking agents are dose dependently associated with the risk of postoperative respiratory complications. In the secondary analysis, the authors evaluated the association between neostigmine dose given for reversal of neuromuscular-blocking agents and respiratory complications. Post hoc, the authors evaluated the effects of appropriate neostigmine reversal (neostigmine ≤ 60 μg/kg after recovery of train-of-four count of 2) on respiratory complications. The authors controlled for patient-, anesthesia-, and surgical complexity-related risk factors. High doses of neuromuscular-blocking agents were associated with an increased risk of postoperative respiratory complications (n = 644) compared with low doses (n = 205) (odds ratio [OR], 1.28; 95% CI, 1.04 to 1.57). Neostigmine was associated with a dose-dependent increase in the risk of postoperative respiratory complications (OR, 1.51; 95% CI, 1.25 to 1.83). Post hoc analysis revealed that appropriate neostigmine reversal eliminated the dose-dependent association between neuromuscular-blocking agents and respiratory complications (for neuromuscular-blocking agent effects with appropriate reversal: OR, 0.98; 95% CI, 0.63 to 1.52). The use of neuromuscular-blocking agents was dose dependently associated with increased risk of postoperative respiratory complications. Neostigmine reversal was also associated with a dose-dependent increase in the risk of respiratory complications. However, the exploratory data analysis suggests that the proper use of neostigmine guided by neuromuscular transmission monitoring results can help eliminate postoperative respiratory complications associated with the use of neuromuscular-blocking agents.

Abstract 336: Selective Use of Neuromuscular Blockade in Therapeutic Hypothermia Does Not Delay Time to Target Temperature

Background: Optimal management of shivering during Therapeutic Hypothermia(TH) is important to quickly achieve target temperature with a goal of improving neurological outcomes. Interventions (pharmacological and non-pharmacological) to manage shivering vary among institutions. We developed a step-wise guideline approach to: 1) prevent and manage shivering during the different phases of TH, 2) avoid delays to achieving target temperature (TT) and 3) reduce the use of neuromuscular blocking agents (NMBA). Methods: We report a single center experience examining the differences in time to target temperature, medication use and patient outcomes pre-(Jan2009-June2011) and post-(July2011-April2013) implementation of a TH Prevention and Management of Shivering algorithm. Results: A total of 138 patients had TH (62 patients pre vs 76 in the post-guidelines). Fewer patients post-guideline implementation received any NMBA (55.3% vs 83.9%, p=0.001), with a lower total dose of NMBA (59.4± 58.7 vs 99.8 ± 70.3 mg, p=0.001). In patients who received NMBA, the post group received more bolus only (64.3% vs 5.8%); and less infusion only (9.5% vs 48.1%) or infusion + bolus (26.2% vs 46.1% p &lt;0.001) therapy. As expected, propofol use increased in the post- group (3.1 vs 2.5 mg/kg/hr, p=0.02) as did increased use of fentanyl boluses (n=44 [4.1 ± 3] vs n=17 [2.5 ± 1.4] p=0.03). While more shivering was noted in the post group (43.5% vs 27.4%; p=0.04), there was no significant difference between the groups in the ROSC to TT time or ICU days. Survival and neurological outcomes were similar between the two groups. Conclusion: Selective use of NMBA as part of a shivering algorithm does not delay time to TT in TH. The decreased use of NMBA resulted in increased doses of sedation and analgesia without effects on patient survival or neurological outcome. Further research on optimal usage of NMBA in TH is needed.

50 Short Term Use of Neuromuscular Blocking Agents in Post Rapid Sequence Intubation Patients Are Not Harmful, and May Be Beneficial

50 Short Term Use of Neuromuscular Blocking Agents in Post Rapid Sequence Intubation Patients Are Not Harmful, and May Be Beneficial

Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose–response relationship

BackgroundSugammadex shows a dose–response relationship for reversal of neuromuscular block (NMB) during propofol anaesthesia. Sevoflurane, unlike propofol, can prolong the effect of neuromuscular blocking agents (NMBAs), increasing recovery time. This open-label, randomized, dose-finding trial explored sugammadex dose–response relationships, safety, and pharmacokinetics when administered for reversal of moderate rocuronium- or vecuronium-induced NMB during sevoflurane maintenance anaesthesia. MethodsAfter anaesthesia induction with propofol, adult patients were randomized to receive single-dose rocuronium 0.9 mg kg−1 or vecuronium 0.1 mg kg−1, with maintenance doses as needed. Anaesthesia was maintained with sevoflurane. NMB was monitored using acceleromyography. After the last dose of NMBA, at reappearance of T2, single-dose sugammadex 0.5, 1.0, 2.0, or 4.0 mg kg−1 or placebo was administered. The primary efficacy variable was time from the start of sugammadex administration to recovery of T4/T1 ratio to 0.9. Safety assessments were performed throughout. ResultsThe per-protocol population comprised 93 patients (rocuronium, n=46; vecuronium, n=47). A statistically significant dose–response relationship was demonstrated for mean recovery times of T4/T1 ratio to 0.9 with increasing sugammadex dose with both NMBAs: rocuronium, 96.3 min (placebo) to 1.5 min (sugammadex 4.0 mg kg−1); vecuronium, 79.0 min (placebo) to 3.0 min (sugammadex 4.0 mg kg−1). Plasma sugammadex concentrations indicated linear pharmacokinetics, independent of NMBA administered. No study drug-related serious adverse events occurred. Evidence of reoccurrence of block was reported in seven patients [sugammadex 0.5 mg kg−1 (suboptimal dose), n=6; 2.0 mg kg−1, n=1]. ConclusionsDuring sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.

Control of perioperative muscle strength during ambulatory surgery

This review describes strategies to control perioperative muscle strength in patients undergoing ambulatory surgery. Although it is impossible to improve muscle relaxation (defined as absence of electrical activity) of intact resting muscle by hypnotics, analgesia is required to prevent pain-evoked muscular contractions during surgery. Regional anesthesia, as well as hypnotics and opioids, promotes intraoperative muscle relaxation. Neuromuscular blocking agents (NMBAs) induce dose-dependent muscle relaxation, but their effects vary widely between individuals, and postoperative residual curarization (PORC) exposes patients to additional risk. Low doses of NMBAs should, therefore, be used, effects be monitored quantitatively by acceleromyography, and residual neuromuscular block be reversed. Acetylcholinesterase inhibitor reversal can cause respiratory side effects, so the lowest efficacious dose should be used: as little as 0.015-0.025 mg kg(-1) of neostigmine is required at a train-of-four count of four with minimal fade. Sugammadex encapsulates steroidal NMBAs. Sugammadex reversal is a viable approach to rapidly antagonize deep levels of neuromuscular block. Optimal muscle relaxation for ambulatory surgery results from a judicious combination of regional anesthesia, opioids, and low doses of NMBAs. The effects of NMBAs should be monitored quantitatively by acceleromyography and reversed appropriately.

Functional recovery after neuromuscular blockade in mechanically ventilated critically ill patients

An estimated 24% to 70% of individuals have prolonged paralysis or severe weakness after receiving neuromuscular blocking agents (NMBAs) when therapy is terminated. The purposes of this study were to (1) evaluate the relationship between recovery of neuromuscular transmission (NMT) and functional muscle activity after NMBA administration; (2) evaluate the relationship between delayed recovery of NMT or muscle activity and functional performance; and (3) determine the predictors of delayed recovery of NMT, muscle activity, and functional performance. This was a multisite study using a prospective, nonexperimental, descriptive design with convenience sampling techniques. Instruments used included a five-point muscle score, Actigraph, and peripheral nerve stimulator. Key findings were as follows: (1) NMT returned promptly, whereas muscle activity remained severely depressed; (2) only two subjects (5%) recovered functional performance within 24 hours; (3) degree of muscle weakness immediately after neuromuscular blockade was associated with prolonged time to extubation and mobility; and (4) predictors of delayed recovery included cumulative dose of aminosteroid NMBAs, age, and renal function. Prolonged recovery of muscle activity and extreme weakness may occur despite brisk recovery of NMT after neuromuscular blockade.

Prospective documentation of sedative, analgesic, and neuromuscular blocking agent use in infants and children in the intensive care unit: A multicenter perspective.

OBJECTIVE: To describe the use of neuromuscular blocking agents (NMBA) in critically ill children. DESIGN: Prospective cohort study. SETTING: Two pediatric intensive care units (ICUs). PATIENTS: All children who received NMBA in the ICUs during the study year. INTERVENTIONS: None Measurements: Data on use of NMBA agents and concurrent use of narcotic and sedative agents were collected. Demographic and outcome information was also obtained. MAIN RESULTS: NMBAs were used for either short-term (<6 hrs) or long-term neuromuscular blockade in 6%-9% of patient ICU days and for long-term blockade in 14%-16% of ventilatory support days. The overall mortality rate among ICU patients who received NMBA was 18%. Choice of agent varied between ICUs; however, succinyl choline was used in only 1% of cases for short-term neuromuscular blockade. The most frequent indication for long-term NMBA use was facilitation of mechanical ventilatory support (49%). Among these children, 46% received high frequency oscillatory ventilation. Long-term neuromuscular blockade was most frequently monitored by clinical examination rather than peripheral nerve stimulation. Paralysis for >6 hrs after discontinuation of NMBA was significantly more common when the agent was administered as an infusion instead of as bolus doses. Myopathy after long-term use of NMBA was seen in only 1 patient (0.4%). Doses (mg/kg) of NMBA did not significantly vary by patient age, but they did increase over time. CONCLUSIONS: Use of NMBA is more common in critically ill children than in reported studies of critically ill adults. Use of NMBA in critically ill children is associated with high severity of illness and mortality rates. Choice of NMBA and method of administration varies among providers. Concurrent use of narcotic and sedative agents with NMBA is frequent, but medication choice also varies among medical providers.