Bertrand Debaene

Residual Paralysis in the PACU after a Single Intubating Dose of Nondepolarizing Muscle Relaxant with an Intermediate Duration of Action

Background Residual neuromuscular blockade remains a problem even after short surgical procedures. The train-of-four (TOF) ratio at the adductor pollicis required to avoid residual paralysis is now considered to be at least 0.9. The incidence of residual paralysis using this new threshold is not known, especially after a single intubating dose of intermediate-duration nondepolarizing relaxant. Therefore, the aim of the study was to determine the incidence of residual paralysis in the postanesthesia care unit after a single intubating dose of twice the ED95 of a nondepolarizing muscle relaxant with an intermediate duration of action. Methods Five hundred twenty-six patients were enrolled. They received a single dose of vecuronium, rocuronium, or atracurium to facilitate tracheal intubation and received no more relaxant thereafter. Neuromuscular blockade was not reversed at the end of the procedure. On arrival in the postanesthesia care unit, the TOF ratio was measured at the adductor pollicis, using acceleromyography. Head lift, tongue depressor test, and manual assessment of TOF and DBS fade were also performed. The time delay between the injection of muscle relaxant and quantitative measurement of neuromuscular blockade was calculated from computerized anesthetic records. Results The TOF ratios less than 0.7 and 0.9 were observed in 16% and 45% of the patients, respectively. Two hundred thirty-nine patients were tested 2 h or more after the administration of the muscle relaxant. Ten percent of these patients had a TOF ratio less than 0.7, and 37% had a TOF ratio less than 0.9. Clinical tests (head lift and tongue depressor) and manual assessment of fade showed a poor sensitivity (11–14%) to detect residual blockade (TOF < 0.9). Conclusion After a single dose of intermediate-duration muscle relaxant and no reversal, residual paralysis is common, even more than 2 h after the administration of muscle relaxant. Quantitative measurement of neuromuscular transmission is the only recommended method to diagnose residual block.

Residual Paralysis after Emergence from Anesthesia

SEVERAL studies have documented that neuromuscular block often persists in the postanesthesia care unit (PACU), even with the administration of acetylcholinesterase inhibitors. The frequency of this phenomenon, which has been called “residual curarization,” “residual neuromuscular block,” “postoperative residual curarization,” or “residual paralysis,” ranges between 4 and 50% depending on the diagnostic criteria, the type of nondepolarizing neuromuscular blocking drug (NMBD), the administration of a reversal agent, and, to a lesser extent, the use of neuromuscular monitoring. The problem is obviously clinically relevant, because residual paralysis after emergence from anesthesia (henceforth referred to as residual paralysis) is associated with muscle weakness, oxygen desaturation, pulmonary collapse, and acute respiratory failure that could lead to severe permanent brain damage or death. Despite extensive documentation of such residual paralysis in the literature, awareness of its clinical consequences remains surprisingly limited, and the use of NMBDs, neuromuscular monitoring, and reversal agents are dictated more by tradition and local practices than by evidence-based medicine. Residual paralysis is associated with postoperative complications such as hypoxia, weakness, and respiratory failure. However, these complications may have many other causes so that the role of neuromuscular block is often unrecognized. Thus, it is important to manage neuromuscular block rationally and have a sound strategy to prevent, diagnose, and treat residual paralysis. This can be accomplished by adhering to simple and consistent guidelines not only before tracheal extubation but also throughout the surgical procedure. The data in the current literature on residual paralysis were obtained with acetylcholinesterase inhibitors as the only agents available to accelerate neuromuscular recovery. Reassessment of practice in this regard is relevant now that sugammadex, a selective binding agent, has become available in certain parts of the world.

Accuracy of a continuous noninvasive hemoglobin monitor in intensive care unit patients.

Objective:To determine whether noninvasive hemoglobin measurement by Pulse CO-Oximetry could provide clinically acceptable absolute and trend accuracy in critically ill patients, compared to other invasive methods of hemoglobin assessment available at bedside and the gold standard, the laboratory analyzer. Design:Prospective study. Setting:Surgical intensive care unit of a university teaching hospital. Patients:Sixty-two patients continuously monitored with Pulse CO-Oximetry (Masimo Radical-7). Interventions:None. Measurements and Results:Four hundred seventy-one blood samples were analyzed by a point-of-care device (HemoCue 301), a satellite lab CO-Oximeter (Siemens RapidPoint 405), and a laboratory hematology analyzer (Sysmex XT-2000i), which was considered the reference device. Hemoglobin values reported from the invasive methods were compared to the values reported by the Pulse CO-Oximeter at the time of blood draw. When the case-to-case variation was assessed, the bias and limits of agreement were 0.0 ± 1.0 g/dL for the Pulse CO-Oximeter, 0.3 ± 1.3g/dL for the point-of-care device, and 0.9 ± 0.6 g/dL for the satellite lab CO-Oximeter compared to the reference method. Pulse CO-Oximetry showed similar trend accuracy as satellite lab CO-Oximetry, whereas the point-of-care device did not appear to follow the trend of the laboratory analyzer as well as the other test devices. Conclusion:When compared to laboratory reference values, hemoglobin measurement with Pulse CO-Oximetry has absolute accuracy and trending accuracy similar to widely used, invasive methods of hemoglobin measurement at bedside. Hemoglobin measurement with pulse CO-Oximetry has the additional advantages of providing continuous measurements, noninvasively, which may facilitate hemoglobin monitoring in the intensive care unit.

The corrugator supercilii, not the orbicularis oculi, reflects rocuronium neuromuscular blockade at the laryngeal adductor muscles.

BackgroundSome studies suggest that the orbicularis oculi is resistant to neuromuscular blocking drugs and behaves like laryngeal muscles. Others report little or no difference between the orbicularis oculi and the adductor pollicis. These discrepancies could be related to the exact site of recording. The purpose of this study was to compare two monitoring sites around the eye with the adductor pollicis and the laryngeal adductor muscles. MethodsAfter institutional approval and informed consent, the evoked response to train-of-four stimulation was measured in 12 patients by acceleromyography at the thumb (adductor pollicis), the eyelid (orbicularis oculi), and the superciliary arch (corrugator supercilii) after 0.5 mg/kg rocuronium during propofol–fentanyl–nitrous oxide anesthesia. In 12 other patients, laryngeal adductor neuromuscular blockade was assessed via the cuff of the tracheal tube and compared with the adductor pollicis and the corrugator supercilii after 0.6 mg/kg rocuronium. ResultsAfter 0.5 mg/kg, maximum blockade (%T1, mean ± SD) was less at the corrugator supercilii (80 ± 20%) than at the adductor pollicis (100 ± 1%) and the orbicularis oculi (93 ± 8%) (P < 0.01). Clinical duration (25%T1) was shorter at the corrugator supercilii (12 ± 7 min) than at the adductor pollicis (25 ± 4 min) and orbicularis oculi (24 ± 10 min) (P < 0.01). After 0.6 mg/kg, maximum blockade was similar at the corrugator supercilii (88 ± 8%) and the laryngeal adductor muscles (89 ± 11%). Clinical duration at the corrugator supercilii and the laryngeal adductors was 17 ± 7 and 17 ± 10 min, respectively. ConclusionsMuscles around the eye vary in their response to rocuronium. The response of the superciliary arch (corrugator supercilii) reflects blockade of laryngeal adductor muscles. However, the eyelid (orbicularis oculi) and thumb (adductor pollicis) have similar sensitivities.

A Randomized, Dose-Response Study of Sugammadex Given for the Reversal of Deep Rocuronium- or Vecuronium-Induced Neuromuscular Blockade Under Sevoflurane Anesthesia

BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. METHODS: We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged ≥20 and <65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T4/T1 ratio to 0.9. RESULTS: The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T4/T1 ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (sd 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. CONCLUSION: Sugammadex at doses of ≥4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia.

Pleth variability index predicts fluid responsiveness in critically ill patients.

Objective:To investigate whether the pleth variability index, a noninvasive and continuous tool, can predict fluid responsiveness in mechanically ventilated patients with circulatory insufficiency. Design:Prospective study. Setting:Surgical intensive care unit of a university hospital. Patients:Forty mechanically ventilated patients with circulatory insufficiency in whom volume expansion was planned by attending physician. Exclusion criteria included spontaneous respiratory activity, cardiac arrhythmia, known intracardiac shunt, severe hypoxemia (Pao2/Fio2 <100 mm Hg), contraindication for passive leg raising, left ventricular ejection fraction of <50%, and hemodynamic instability during the procedure. Interventions:Fluid challenge with 500 mL of 130/0.4 hydroxyethyl-starch if respiratory variations in arterial pulse pressure were ≥13% or with passive leg raising if variations in arterial pulse pressure were <13%. Measurements and Main Results:Pleth variability index, variations in arterial pulse pressure, and cardiac output estimated by echocardiography were recorded before and after fluid challenge. Fluid responsiveness was defined as an increase in cardiac output of ≥15%. Twenty-one patients were responders and 19 were nonresponders. Mean ± sd pleth variability index (28% ± 13% vs. 11% ± 4%) and arterial pulse pressure variation (22% ± 11% vs. 5% ± 2%) values at baseline were significantly higher in responders than in nonresponders. The pleth variability index threshold value of 17% allowed discrimination between responders and nonresponders with a sensitivity of 95% (95% confidence interval, 74% to 100%) and a specificity of 91% (95% confidence interval, 70% to 99%). The pleth variability index at baseline correlated (r = .72, p < .0001) with the percentage change in cardiac output induced by fluid challenge, suggesting that a higher pleth variability index at baseline will correlate with a higher percentage change in cardiac output after volume expansion. Conclusions:The pleth variability index can predict fluid responsiveness noninvasively in intensive care unit patients under mechanical ventilation.

Monitoring the onset of neuromuscular block at the orbicularis oculi can predict good intubating conditions during atracurium-induced neuromuscular block.

This study was designed to assess whether monitoring the orbicularis oculi (OO) can predict good tracheal intubating conditions.Fifty patients, ASA grade I or II were studied. Anesthesia was induced with thiopental (5 mg/kg) and fentanyl (3 micro gram/kg). The ulnar and facial nerves were simultaneously stimulated using train-of-four (TOF) stimulations every 10 s. The responses of the adductor pollicis (AP) and the OO were estimated visually. Patients were randomly allocated to receive either atracurium 0.5 mg/kg (n = 30) or 0.3 mg/kg (n = 20). In each group, endotracheal intubation was performed randomly when the OO or the AP was completely blocked. If complete block was not obtained, intubation was performed 300 s after administration of atracurium. Intubating conditions were scored on a 1 to 4 scale. All intubations were performed by the same physician unaware of the dose and the muscular responses. After 0.5 mg/kg, both muscles were completely blocked in all patients. The average onset time (time from the injection of atracurium to the disappearance of all muscular responses after TOF) was shorter at the OO (2.35 +/- 0.12 min) than at the AP (3.59 +/- 0.15 min) (P < 0.001) (mean +/- SD). Endotracheal intubating conditions were comparable in both groups: good or excellent after 0.5 mg/kg. After 0.3 mg/kg, complete block was achieved only 2/20 at the OO and 12/20 at the AP. Intubating conditions were comparable in both groups: poor or inadequate, except in the two patients with complete OO block, for whom conditions were good. It is concluded that OO monitoring can predict good intubating conditions earlier than AP monitoring when using 0.5 mg/kg but not 0.3 mg/kg atracurium. (Anesth Analg 1995;80:360-3)

Muscle relaxation and increasing doses of propofol improve intubating conditions.

PurposeMuscle relaxants and anesthetics are usually associated during intubation. However, their relative role to facilitate the process is not dearly defined. This study was designed to determine, during intubation: i) the relative role of anesthetics and atracurium-induced neuromuscular block and; ii) the effect of different doses of propofol in the presence of complete muscle block.MethodsPatients were randomized to four groups and received fentanyl and a standardized anesthetic procedure. Patients from groups high (H;n = 45), medium (M;n = 48) and low(L;n = 47) received 2.5 mg· kg−1, 2.0 mg· kg−1, and 1.5 mg· kg−1 of propofol respectively, Atracurium (0.5 mg· kg−1) was then injected and tracheal intubation performed once complete block was achieved at the orbicularis oculi. Patients from group without atracurium (WA;n = 20) received propofol as in group H. Intubation was performed at the expected onset time of action of atracurium.ResulteUsing the same dose of propofol, the incidence of good or excellent intubating conditions was 35% without atracurium and 95% with atracurium (P < 0,0001), In patients receiving atracurium, clinically acceptable intubating conditions were more frequently achieved in groups receiving the highest propofol doses (group H or M vs group L;P < 0.03).ConclusionOur study confirms the interaction between anesthesia and muscle relaxation to produce adequate intubating conditions. In the conditions described, intubating conditions were more dependent on atracurium-induced neuromuscular blockade than on anesthetics, but both atracurium and propofol improved intubating conditions.RésuméObjectifAgents d’anesthésie et curares sont souvent associés pour l’intubation. Cependant, leurs rôles respectifs pendant l’intubation ne sont pas clairement définis. Cette étude a pour objectif de différencier pour l’intubation i) l’effet des agents d’anesthésie de ceux du bloc moteur induit par l’atracurium et ii) le rôle de différentes doses de propofol couplées à un bloc moteur complet induit par l’atracurium.MéthodeLes patients étaient randomisés en quatre groupes. Tous recevaient du fentanyl et une procédure d’anesthésie standardisée. Les patients des groupes high (H; n = 45), medium (M; n = 48), et low (L; n = 47) recevaient respectivement 2,5 mg· kg−1, 2,0 mg· kg−1 et 1,5 mg· kg−1 de propofol puis atracurium 0,5 mg· kg−1. Lintubation était réalisée et cotée après qu’un bloc complet avait été obtenu à l’orbiculaire de l’œil. Les patients du groupe n’ayant pas reçu l’atracurium (WA) recevaient le propofol comme dans le groupe H, et étaient intubés après un intervalle de temps correspondant à celui du délai d’action supposé de l’atracurium.RésultatsChez les patients recevant des doses d’anesthésie équivalentes, les conditions d’intubation étaient significativement meilleures chez ceux recevant l’atracurium (groupe H) par rapport aux patients WA (P < 0,0001). Pour les patients recevant de l’atracurium, les conditions d’intubation étaient significativement meilleures chez les patients du groupe H ou M par rapport aux patients du groupe L (P < 0,03).ConclusionLes conditions d’intubation dépendent plus du bloc neuromusculaire que des agents d’anesthésie lorsque l’on attend l’installation complète du bloc. Cependant, les conditions d’intubation dépendent aussi du rôle des agents d’anesthésie lors de l’intubation avec une curarisation complète.

ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans

Background: ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis. Methods: In 30 adults, anesthesia was induced with propofol (2–5 mg/kg) and fentanyl (2–3 micro gram/kg). After train‐of‐four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group). Results: Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/‐ 16 s, 62 +/‐ 13 s, and 52 +/‐ 14 s (mean +/‐ SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/‐ 33 s, 96 +/‐ 20 s, and 82 +/‐ 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P <0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/‐ 15% vs. 94 +/‐ 4% after 0.75 mg/kg; 86 +/‐ 7% vs. 97 +/‐ 4% after 1.5 mg/kg; and 91 +/‐ 5% vs. 99 +/‐ 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/‐ 2.2 min versus 10.2 +/‐ 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/‐ 3.7 min at the vocal cords and at 18.3 +/‐ 5.2 min at the adductor pollicis muscle. Conclusions: ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.

The effect of nefopam on morphine overconsumption induced by large-dose remifentanil during propofol anesthesia for major abdominal surgery.

Opioids may activate pain facilitatory systems opposing analgesia. We investigated whether large-dose remifentanil given during IV anesthesia caused postoperative morphine overconsumption and whether nefopam (a centrally acting analgesic) could reduce this. Sixty patients scheduled for abdominal surgery were included in this prospective, randomized study. The first 30 patients received either small-dose (Group S: 3 ng/mL) or large-dose (Group L: 8 ng/mL) remifentanil administrated by a target-controlled infusion during propofol anesthesia. Before skin closure, patients received morphine 0.15 mg/kg. Another 30 patients also received nefopam 20 mg intraoperatively. Postoperative pain was controlled by titration of morphine, followed by patient-controlled morphine analgesia (PCA). Morphine was requested earlier in Group L than in Group S (10 [1–63] min versus 37 [5–90] min, median [range]; P < 0.002). The dose of morphine by titration was larger in Group L than in Group S (0.28 [0.04–0.38] mg/kg versus 0.16 [0.03–0.41] mg/kg; P < 0.05). PCA morphine consumption and pain scores were similar. There were no differences between the nefopam groups in the time to first morphine request or in the dose of morphine by titration. Postoperative morphine overconsumption occurred after large-dose remifentanil and propofol anesthesia during the early postoperative period. Pretreatment with nefopam could be useful to prevent pain sensitization induced by opioids.