Michael J. Avram

Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit

BACKGROUND: Incomplete recovery of neuromuscular function may impair pulmonary and upper airway function and contribute to adverse respiratory events in the postanesthesia care unit (PACU). The aim of this investigation was to assess and quantify the severity of neuromuscular blockade in patients with signs or symptoms of critical respiratory events (CREs) in the PACU. METHODS: We collected data over a 1-yr period. PACU nurses identified patients with evidence of a predefined CRE during the first 15 min of PACU admission. Train-of-four (TOF) ratios were immediately quantified in these patients using acceleromyography (cases). TOF data were also collected in a control group that consisted of patients undergoing a general anesthetic during the same period who were matched with the cases by age, sex, and surgical procedure. RESULTS: A total of 7459 patients received a general anesthetic during the 1-yr period, of whom 61 developed a CRE. Forty-two of these cases were matched with controls and constituted the study group for statistical analysis. The most common CREs among matched cases were severe hypoxemia (22 of 42 patients; 52.4%) and upper airway obstruction (15 of 42 patients; 35.7%). There were no significant differences between the cases and matched controls in any measured preoperative or intraoperative variables. Mean (±sd) TOF ratios were 0.62 (±0.20) in the cases, with 73.8% of the cases having TOF ratios <0.70. In contrast, TOF values in the controls were 0.98 (±0.07) (a difference of −0.36 with a 95% confidence interval of −0.43 to −0.30, P < 0.0001), and no control patients were observed to have TOF values <0.70 (the 95% confidence interval of the difference was 59%–85%, P < 0.0001). CONCLUSIONS: A high incidence of severe residual blockade was observed in patients with CREs, which was absent in control patients without CREs. These findings suggest that incomplete neuromuscular recovery is an important contributing factor in the development of adverse respiratory events in the PACU.

Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit.

Background:Incomplete recovery from neuromuscular blockade in the postanesthesia care unit (PACU) may contribute to adverse postoperative respiratory events. This study determined the incidence and degree of residual neuromuscular blockade in patients randomized to conventional qualitative train-of-four (TOF) monitoring or quantitative acceleromyographic monitoring. The incidence of adverse respiratory events in the PACU was also evaluated. Methods:One hundred eighty-five patients were randomized to intraoperative acceleromyographic monitoring (acceleromyography group) or qualitative TOF monitoring (TOF group). Anesthetic management was standardized. TOF patients were extubated when standard criteria were met and no fade was observed during TOF stimulation. Acceleromyography patients had a TOF ratio of greater than 0.80 as an additional extubation criterion. Upon arrival in the PACU, TOF ratios of both groups were measured with acceleromyography. Adverse respiratory events during transport to the PACU and during the first 30 min of PACU admission were also recorded. Results:A lower frequency of residual neuromuscular blockade in the PACU (TOF ratio ≤ 0.9) was observed in the acceleromyography group (4.5%) compared with the conventional TOF group (30.0%; P < 0.0001). During transport to the PACU, fewer acceleromyography patients developed arterial oxygen saturation values, measured by pulse oximetry, of less than 90% (0%) or airway obstruction (0%) compared with TOF patients (21.1% and 11.1%, respectively; P < 0.002). The incidence, severity, and duration of hypoxemic events during the first 30 min of PACU admission were less in the acceleromyography group (all P < 0.0001). Conclusions:Incomplete neuromuscular recovery can be minimized with acceleromyographic monitoring. The risk of adverse respiratory events during early recovery from anesthesia can be reduced by intraoperative acceleromyography use.

The Pharmacokinetics of Dexmedetomidine in Volunteers with Severe Renal Impairment

Dexmedetomidine, an &agr;2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 &mgr;g/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 ± 0.55 and 1.54 ± 0.08 L/kg, respectively; mean ± sd) or elimination clearance (12.5 ± 4.6 and 8.9 ± 0.7 mL · min−1 · kg−1, respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 ± 11.3 vs 136.5 ± 13.0 min;P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time.

Gastric Emptying of Water in Term Pregnancy

Background Healthy nonpregnant patients may ingest clear liquids until 2 h before induction of anesthesia without adversely affecting gastric volume. The purpose of this study was to compare gastric emptying in term, nonlaboring pregnant women after ingestion of 50 ml water (control) with that after ingestion of 300 ml water. Methods Gastric emptying was assessed in healthy, nonobese, term pregnant volunteers using both serial gastric ultrasound examinations (n = 9) and acetaminophen absorption (n = 11) in a crossover study design. After an overnight fast, volunteers ingested 1.5 g acetaminophen and 50 or 300 ml water (assigned in random order) on two occasions separated by at least 2 days. Serial gastric antrum cross-sectional areas were determined using gastric ultrasound imaging, and the half-time to gastric emptying was calculated. Serial plasma acetaminophen concentrations were measured. Areas under the plasma acetaminophen concentration versus time curve, peak concentrations, and time to peak concentration for 50- and 300-ml ingestions were compared. Results Gastric emptying half-time was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (24 ± 6 vs. 33 ± 8 min). There were no differences in acetaminophen areas under the curve at 60, 90, or 120 min, or in acetaminophen peak concentration. Time to peak concentration of acetaminophen was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (25 ± 12 vs. 41 ± 19 min). Conclusions Gastric emptying in healthy, term, nonobese, nonlaboring pregnant women is not delayed after ingestion of 300 ml water compared with that after an overnight fast.

Residual paralysis at the time of tracheal extubation

Respiratory and pharyngeal muscle function are impaired during minimal neuromuscular blockade. Tracheal extubation in the presence of residual paresis may contribute to adverse respiratory events. In this investigation, we assessed the incidence and severity of residual neuromuscular block at the time of tracheal extubation. One-hundred-twenty patients presenting for gynecologic or general surgical procedures were enrolled. Neuromuscular blockade was maintained with rocuronium (visual train-of-four [TOF] count of 2) and all subjects were reversed with neostigmine at a TOF count of 2–4. TOF ratios were quantified using acceleromyography immediately before tracheal extubation, after clinicians had determined that complete neuromuscular recovery had occurred using standard clinical criteria (5-s head lift or hand grip, eye opening on command, acceptable negative inspiratory force or vital capacity breath values) and peripheral nerve stimulation (no evidence of fade with TOF or tetanic stimulation). TOF ratios were measured again on arrival to the postanesthesia care unit. Immediately before tracheal extubation, the mean TOF ratio was 0.67 ± 0.2; among the 120 patients, 70 (58%) had a TOF ratio <0.7 and 105 (88%) had a TOF ratio <0.9. Significantly fewer patients had TOF ratios <0.7 (9 subjects, 8%) and <0.9 (38 subjects, 32%) in the postanesthesia care unit compared with the operating room (P < 0.001). Our results suggest that complete recovery from neuromuscular blockade is rarely present at the time of tracheal extubation.

Postanesthesia care unit recovery times and neuromuscular blocking drugs: a prospective study of orthopedic surgical patients randomized to receive pancuronium or rocuronium.

In this study, we examined the effect of choice of neuromuscular blocking drug (NMBD) (pancuronium versus rocuronium) on postoperative recovery times and associated adverse outcomes in patients undergoing orthopedic surgical procedures. Seventy patients were randomly allocated to a pancuronium or rocuronium group. On arrival to the postanesthesia care unit (PACU) and again 30 min later, train-of-four ratios were quantified by using acceleromyography. Immediately after acceleromyographic measurements, patients were assessed for signs and symptoms of residual paresis. During the PACU admission, episodes of hypoxemia, nausea, and vomiting were recorded. The time required for patients to meet discharge criteria and the time of actual PACU discharge were noted. Forty percent of patients in the pancuronium group had train-of-four ratios <0.7 on arrival to the PACU, compared with only 5.9% of subjects in the rocuronium group (P < 0.001). Patients in the pancuronium group were more likely to experience symptoms of muscle weakness (blurry vision and generalized weakness; P < 0.001) and hypoxemia (10 patients in the rocuronium group versus 21 patients in the pancuronium group; P = 0.015) during the PACU admission. Significant delays in meeting PACU discharge criteria (50 min [45–60 min] versus 30 min [25–40 min]) and achieving actual discharge (70 min [60–90 min] versus 57.5 min [45–61 min]) were observed when the pancuronium group was compared with the rocuronium group (P < 0.001). In conclusion, our study indicates that PACU recovery times may be prolonged when long-acting NMBDs are used in surgical patients.

Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk.

Lactating women undergoing operations requiring general anesthesia are advised to pump and discard their milk for 24 hours after the procedure. Data on anesthetic drug transfer into breast milk are limited. This study determined the pharmacokinetics of midazolam, propofol, and fentanyl transfer into milk to provide caregivers with data regarding the safety of breast milk after administration of these drugs.

Using Front-end Kinetics to Optimize Target-controlled Drug Infusions

Background The mode of drug administration, blood sampling schedule, and sampling site affect the pharmacokinetic model derived. The present study tested the hypothesis that three-compartment pharmacokinetic model parameters derived from arterial drug concentrations obtained after rapid intravenous administration can be used to design a target-controlled drug infusion (TCI) that deviates minimally from the target. Methods Arterial thiopental concentration data obtained from the moment of injection in a previous study of five dogs were used. Three three-compartment models were constructed, one based on early concentrations classically obtained at 1, 2, and 3 min; another using all concentrations obtained beginning with the thiopental recirculation peak; and the last with the initial distribution volume (VC) fixed to the sum of VC and the nondistributive volume of the recirculatory model from the earlier study. Using these models, TCIs were designed that would maintain 20 &mgr;g/ml thiopental concentrations in VC for 60 min if simulated with the models used in their design. Drug concentrations resulting from these TCIs were then simulated using recirculatory model kinetics, and prediction errors were evaluated. Results Models with VCs estimated from intermittent or frequent early blood concentrations overestimated not only VC but also the volume and clearance of the rapidly equilibrating tissues, and their TCIs significantly overshot the target. With VC fixed to recirculatory model parameters, drug distribution was described in a manner consistent with that of the recirculatory model, and the TCI deviated minimally from the target. A similar three-compartment model was derived from data obtained from a simulation of a 2-min infusion using recirculatory kinetic parameters. Conclusions Because three-compartment models based on drug concentration histories obtained after rapid intravenous administration do not characterize VC accurately, TCIs based on them produce concentrations exceeding the target. A model capable of producing TCIs deviating minimally from the target can be derived from data obtained during and after a brief drug infusion.

What determines anesthetic induction dose? It's the front-end kinetics, doctor!

ince IV anesthetics were first used to inducegeneral anesthesia, choosing the appropriatedose has been a combination of the art and sci-ence of the specialty. The dramatic evidence of thepotential consequences of this dosing challenge is per-haps best illustrated by the tragic outcomes of theadministration of a “standard dose” of thiopental tothe hypovolemic victims of the Japanese attack onPearl Harbor (1). Until recently, little has been accom-plished to improve the scientific basis of dosageselection.Fisher (2), in his editorial, “(Almost) everything youlearned about pharmacokinetics was (somewhat)wrong!” presented some of the problems associatedwith the application of conventional pharmacokineticcompartmental modeling to situations in which theplasma concentrations of the drug are changing rap-idly. In this editorial, we shall examine various ap-proaches to modeling

Age-stratified pharmacokinetics of ketorolac tromethamine in pediatric surgical patients

Published data suggest that ketorolac pharmacokinetics are different in children than in adults. We sought to better characterize ketorolac pharmacokinetics in children. Thirty-six children, aged 1–16 yr, were stratified into four age groups: 1–3 yr, 4–7 yr, 8–11 yr, and 12–16 yr. Each child received 0.5 mg/kg of ketorolac tromethamine IV after completion of elective surgery. A maximum of 16 venous blood samples (mean, 13 ± 2) were collected at predetermined times up to 10 h after drug administration. Plasma ketorolac concentrations were measured by high-performance liquid chromatography after solid-phase extraction. Individual concentration-versus-time relationships were best fit to a two-compartment pharmacokinetic model by using SAAM II. Body weight-normalized pharmacokinetic variables did not differ among the age groups and were similar to those reported for adults, including a volume of distribution at steady state of 113 ± 33 mL/kg (mean ± sd) and an elimination clearance of 0.57 ± 0.17 mL · min−1 · kg−1. Our study demonstrates that a single dose of ketorolac (0.5 mg/kg) results in plasma concentrations in the adult therapeutic concentration range for 6 h in most children. Our data provide no evidence that children require either larger weight-adjusted doses or shorter dosing intervals than adults to provide similar plasma drug concentrations.