Matthias Eikermann

Accelerometry of Adductor Pollicis Muscle Predicts Recovery of Respiratory Function from Neuromuscular Blockade

Background Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers. Methods Rocuronium (0.01 mg/kg + 2–10 &mgr;g · kg−1 · min−1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with “acceptable” pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of ≥90% of baseline) was calculated using a linear regression model. Results At peak blockade (TOF ratio 0.5 ± 0.16), forced inspiratory flow was impaired (53 ± 19%) to a greater degree than forced expiratory flow (75 ± 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 ± 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22–0.71) predicts “acceptable” recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82–1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively. Conclusion Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8), and extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from neuromuscular blockade, respiratory function can still be impaired.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.

Background:Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. Methods:A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. Results:Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. Conclusion:Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.

Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study

Objective To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. Design Prospective, propensity score matched cohort study. Setting General teaching hospital in Boston, Massachusetts, United States, 2006-10. Participants 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measures The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation <90% with a decrease in oxygen saturation after extubation of >3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. Results The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). Conclusion The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited.

Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery room discharge

BACKGROUND Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay. METHODS At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds. RESULTS PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission. CONCLUSIONS PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In our system, PORC increases the chances of patients having to wait to enter the PACU.

Diaphragm muscle thinning in patients who are mechanically ventilated.

BACKGROUND Approximately 40% of patients in medical ICUs require mechanical ventilation (MV). Approximately 20% to 25% of these patients will encounter difficulties in discontinuing MV. Multiple studies have suggested that MV has an unloading effect on the respiratory muscles that leads to diaphragmatic atrophy and dysfunction, a process called ventilator-induced diaphragmatic dysfunction (VIDD). VIDD may be an important factor affecting when and if MV can be discontinued. A sensitive and specific diagnostic test for VIDD could provide the physician with valuable information that might influence decisions regarding extubation or tracheostomy. The purpose of this study was to quantify, using daily sonographic assessments, the rate and degree of diaphragm thinning during MV. METHODS Seven intubated patients receiving MV during acute care were included. Using sonography, diaphragm muscle thickness was measured daily from the day of intubation until the patient underwent extubation or tracheostomy or died. We analyzed our data using standard descriptive statistics, linear regression, and mixed-model effects. RESULTS The overall rate of decrease in the diaphragm thickness of all seven patients over time averaged 6% per day of MV, which differed significantly from zero. Similarly, the diaphragm thickness decreased for each patient over time. CONCLUSION Sonographic assessment of the diaphragm provides noninvasive measurement of diaphragmatic thickness and the degree of diaphragm thinning in patients receiving MV. Our data show that diaphragm muscle thinning starts within 48 h after initiation of MV. However, it is unclear if diaphragmatic thinning correlates with diaphragmatic atrophy or pulmonary function. The relationship between diaphragm thinning and diaphragm strength remains to be elucidated.

Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study

Objective To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Design Hospital based registry study. Setting Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. Participants 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Interventions Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. Main outcome measure Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Results Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. Conclusions Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.

Incidence and duration of residual paralysis at the end of surgery after multiple administrations of cisatracurium and rocuronium

In a randomised, controlled, double‐blind, multicentre trial in 338 patients, we assessed the incidence of residual paralysis following administration of cisatracurium or rocuronium. The incidence at the end of surgery was significantly lower in patients treated with rocuronium (62 of 142 patients, 44%) than in those given cisatracurium (99 of 175 patients, 57%) (p < 0.05). In contrast, with rocuronium the mean (SD) time between skin closure and extubation was 28 (28) min vs 18 (19) min for cisatracurium, and the duration 0.9 (time from administration of last top‐up dose to recovery of the train‐of‐four ratio to 0.9) was significantly longer and more variable for rocuronium than for cisatracurium. Thus, after repeated administration, the duration and variability of duration of action are greater with rocuronium compared with cisatracurium. These pharmacodynamic differences do not necessarily translate into a higher incidence of residual paralysis, because clinicians compensate for the longer duration of action and variability of rocuronium by terminating administration of the neuromuscular blocking earlier.

Development and validation of a score for prediction of postoperative respiratory complications.

Background:Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care. Methods:Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated. Results:In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their &bgr; coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55–1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation. Conclusion:The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications.

Unwarranted Administration of Acetylcholinesterase Inhibitors Can Impair Genioglossus and Diaphragm Muscle Function

Background:It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume. Methods:The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9). Results:Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram (to 70.3 ± 7.6, 49.2 ± 3.2, and 39.7 ± 2.3% of control, respectively), decreases in diaphragm electromyogram (to 103.1 ± 6.5, 83.1 ± 4.7, and 68.7 ± 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 ± 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 ± 3% of control, whereas end-expiratory lung volume remained constant. Conclusions:The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block.

Early Mobilization in Critically Ill Patients: Patients' Mobilization Level Depends on Health Care Provider's Profession

To evaluate whether the level of mobilization achieved and the barriers for progressing to the next mobilization level differ between nurses and physical therapists.