Vera Saldien

Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics

Background:Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods:Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied. Results:The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58–74% after 4–8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively. Conclusions:In male subjects, sugammadex safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium in a dose-dependent manner. Sugammadex enhanced the renal excretion of rocuronium, and its clearance is approximately one third that of rocuronium.

Reversal of rocuronium-induced neuromuscular block with the novel drug sugammadex is equally effective under maintenance anesthesia with propofol or sevoflurane

In this study we investigated whether the novel reversal drug, sugammadex, is equally effective at reversing rocuronium-induced neuromuscular block (NMB) in patients under propofol or sevoflurane maintenance anesthesia. After receiving propofol for induction, patients were randomized to propofol (n = 21) or sevoflurane (n = 21). Rocuronium 0.6 mg/kg was administered for tracheal intubation. NMB was monitored using acceleromyography. At reappearance of the second twitch of the train-of-four ratio, sugammadex 2.0 mg/kg was administered by IV bolus. The primary end-point was time from start of sugammadex administration to recovery of train-of-four ratio to 0.9. Mean recovery time was 1.8 min after both propofol and sevoflurane anesthesia. The 95% confidence interval for the difference in recovery time between the 2 groups (–0.5 to +0.4 min) was well within the predefined equivalence interval (–1 to +1 min), indicating that recovery from NMB was unaffected by maintenance anesthesia. Thirteen patients (propofol n = 4; sevoflurane n = 9) experienced adverse events; these were treatment-related in 4 patients (propofol n = 3; sevoflurane n = 1). There were no treatment-related serious adverse events and no discontinuations or deaths. No residual paralysis occurred. The safety profile of sugammadex was somewhat more favorable under propofol than under sevoflurane anesthesia.

Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section.

In a double-blind, randomized trial, 98 parturients undergoing cesarean section received either hyperbaric or plain bupivacaine 6.6 mg combined with sufentanil 3.3 [micro sign]g as part of a combined spinal-epidural procedure. To prevent hypotension, 1000 mL of lactated Ringers solution, 500 mL of hydroxyethyl starch 6%, and ephedrine 5 mg were administered IV. The height of the block was equal in both groups, but more patients in the plain group had blocks that were either too high or too low (P < 0.01). The number of patients requiring epidural supplementation was equal in both groups. Strict criteria were used to treat hypotension. The overall incidence of systolic blood pressure (<90 mm Hg) was 13%, whereas it was more pronounced in the plain group (21% vs 6% in the hyperbaric group, P < 0.05), which required more ephedrine (P < 0.05) and in which a greater incidence of nausea was noticed (P < 0.05). We conclude that the use of a small dose of intrathecal bupivacaine combined with sufentanil plus our described preloading regimen resulted in a lower incidence of hypotension. Further, we conclude that the use of hyperbaric bupivacaine in this manner provides a more reliable block and a lower incidence of hypotension than plain bupivacaine. Implications: A small dose of hyperbaric bupivacaine 0.5% combined with sufentanil used intrathecally during cesarean section offered a more reliable cephalad spread of the spinal block than the glucose-free combination, which was reflected in a lower incidence of hypotension and nausea. (Anesth Analg 1998;86:989-93)

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.

Drug‐induced sleep endoscopy in sleep‐disordered breathing: Report on 1,249 cases

To describe upper airway (UA) collapse patterns during drug‐induced sleep endoscopy (DISE) in a large cohort of patients with sleep‐disordered breathing (SDB) and to assess associations with anthropometric and polysomnographic parameters.

Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome

The aim of this study was to assess the value of drug‐induced sleep endoscopy (DISE) using a custom‐made simulation bite in maximal comfortable protrusion (MCP) of the mandible, in the prediction of treatment outcome for obstructive sleep apnea (OSA) with a mandibular advancement device (MAD). Two hundred patients (74% male; age 46 ± 9 years; apnea–hypopnea index [AHI] 19 ± 13 h−1 sleep; body mass index [BMI] 27 ± 4 kg m−2) with sleep‐disordered breathing underwent DISE with a simulation bite in MCP. One hundred and thirty‐five patients with an established diagnosis of OSA commenced MAD treatment. The associations between the findings during DISE with simulation bite and treatment outcome were evaluated. Treatment response was defined as a reduction in AHI following MAD treatment of ≥ 50% compared to baseline. Overall MAD treatment response in the studied population was 69%. The results of this study demonstrated a statistically significant association between a positive effect of the simulation bite on the upper airway patency during DISE and treatment response with MAD (P < 0.01). The results of this study suggest that the use of a simulation bite in maximal comfortable protrusion (MCP) of the mandible, as used during DISE in patients with OSA, tends to be effective in predicting treatment response of MAD treatment.

Drug-induced sedation endoscopy in pediatric obstructive sleep apnea syndrome

AIM To describe the pattern of upper airway (UA) obstruction during drug-induced sedation endoscopy (DISE) and to evaluate the outcome of DISE-directed treatment. METHODS Prospective study of DISE in surgically naive obstructive sleep apnea syndrome (OSAS) children without syndromic comorbidity or craniofacial abnormalities. Treatment was individually tailored according to UA findings during DISE and polysomnographic data. Reported values are median (lower-upper quartile). RESULTS Thirty-seven children aged 4.1 years (2.1-6.0), with body mass index z-score 0.3 (-0.9 to 0.9), and obstructive apnea-hypopnea index (oAHI) 9.0/h (6.1-19.3) were included. Adenotonsillar obstruction was found in 33 cases (89%) as an isolated entity or as part of a multi-level obstruction. These children were treated with adenotonsillectomy (n = 28), adenoidectomy (n = 3), or tonsillectomy (n = 2). The remaining four patients received non-surgical treatment. Pre-postoperative polysomnographic data in 22 patients showed a significant improvement in oAHI from 8.6/h (6.7-20.7) to 1.0/h (0.6-2.0) (P = 0.001). Only two of these 22 children had residual OSAS (oAHI ≥ 5/h), indicating a success rate of 91%. CONCLUSIONS Based on UA findings during DISE, a non-surgical treatment was proposed for 11% of children. A 91% success rate was obtained in those treated with (adeno)tonsillectomy. These data suggest that DISE may be helpful to identify patients most likely to benefit from UA surgery.

Drug-induced sedation endoscopy in surgically naive children with Down syndrome and obstructive sleep apnea

OBJECTIVE To describe the pattern of upper airway (UA) obstruction in surgically naive children with Down syndrome and obstructive sleep apnea (OSA), and to evaluate the outcome of drug-induced sedation endoscopy (DISE)-directed treatment. METHODS A prospective study of DISE in surgically naive children with Down syndrome and OSA was performed. Treatment was individually tailored based on the DISE findings and was evaluated by control polysomnography (PGS). Results are presented as median (lower-upper quartile) unless otherwise stated. RESULTS In 41 children, aged 4.2 years (range, 2.8-6.0) with a body mass z score of 1.04 (-0.55 to 1.82) and obstructive apnea-hypopnea index (oAHI) of 10.1/h (range, 6.3-23.0), DISE was performed. Adeno-/tonsillar obstruction was found in 75.6% of the patients, and these patients subsequently underwent UA surgery. Seven patients were non-surgically treated, and three received a combined treatment. A multilevel collapse was present in 85.4%. Tongue base obstruction was present in ten patients (24.4%) and epiglottic collapse in 48.8%. Pre- and postoperative PSG data were available for 25 children (adenotonsillectomy, n = 16; tonsillectomy, n = 7; adenoidectomy, n = 2). A significant improvement in oAHI from 11.4/h (range, 7.7-27.0) to 5.5/h (range, 2.1-7.6) was found. Persistent OSA was present in 52% of the children. No significant association between different DISE findings and persistent OSA could be found. CONCLUSION Most patients with Down syndrome and OSA present with multilevel collapse on DISE. Adenotonsillectomy results in a significant improvement of the oAHI; however more than half of the patients had persistent OSA, probably due to multilevel collapse. Upper airway evaluation may provide more insights into the pattern of UA obstruction in patients with persistent OSA.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

BACKGROUND The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING District general hospital in Belgium. PARTICIPANTS Twelve healthy male volunteers. INTERVENTIONS Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg−1, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg−1 (n = 6) or neostigmine 70 &mgr;g kg−1 (n = 6). MAIN OUTCOME MEASURES EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) &mgr;V in the neostigmine group and 1.6 (1.3 to 1.9) &mgr;V in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 &mgr;V vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION EudraCT ref: 2013-002078-30.

Acute respiratory distress after upper airway obstruction following palatoplasty

We report a case of acute respiratory distress after upper airway obstruction following routine palatoplasty in an otherwise healthy 6-year-old boy. We believe that extreme variation of intrathoracal pressure was the basis of the development of the acute respiratory distress. We recommend after palatoplasty a more than careful postoperative clinical observation to detect and treat postoperative obstruction and hypoxemia.