Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects.

BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 µg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1-0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch(®) SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 µg/kg plus atropine 10-20 µg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3-1.5) min and 6.7 (5.5-8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB. CONCLUSION: Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 µg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00825812.

Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial.

BACKGROUND: Sugammadex, a specifically designed gamma-cyclodextrin, is a selective relaxant binding drug that rapidly reverses rocuronium-induced and, to a lesser extent, vecuronium-induced neuromuscular blockade. In this study, we compared the efficacy of sugammadex and neostigmine for the reversal of vecuronium-induced neuromuscular blockade in patients scheduled for elective surgery. METHODS: Patients aged > or = 18 yr, ASA Class I-III, and scheduled for a surgical procedure under sevoflurane/opioid anesthesia received an intubating dose of vecuronium (0.1 mg/kg) and maintenance doses of 0.02-0.03 mg/kg at reappearance of the second twitch (T(2)) of train-of-four (TOF) if required. Neuromuscular blockade was monitored using acceleromyography (TOF-Watch SX, Schering-Plough Ireland, Dublin, Ireland). At end of surgery, at reappearance of T(2) after the last dose of vecuronium, patients were randomized to receive either sugammadex (2 mg/kg) or neostigmine (50 microg/kg) plus glycopyrrolate (10 microg/kg) i.v.. The primary efficacy end-point was time from start of administration of sugammadex or neostigmine to recovery of TOF ratio to 0.9. RESULTS: The geometric mean time to recovery of the TOF ratio to 0.9 was significantly faster with sugammadex compared with neostigmine (2.7 min [95% confidence interval {CI}]: 2.2-3.3) versus 17.9 min [95% CI: 13.1-24.3], respectively; P < 0.0001). The mean recovery times to a TOF ratio of 0.8 and 0.7 were also significantly shorter with sugammadex. No serious adverse events or unexpected side effects were reported with either drug. CONCLUSION: Sugammadex provided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine.

Lower limb compartment syndrome as a complication of laparoscopic laser surgery for severe endometriosis.

OBJECTIVE: To report a case of lower limb compartment syndrome (LLCS) during long duration laparoscopic interventions for resection of extensive endometriosis, and evaluate the efficiency of a novel patient positioning method to reduce its prevalence. DESIGN: Case report and observational study. SETTING: University Hospitals, Belgium. PATIENT(S): Thirty-year-old woman undergoing a long duration laparoscopic intervention for resection of stage IV pelvic endometriosis. INTERVENTION(S): Laparoscopic intervention for resection of stage IV pelvic endometriosis. MAIN OUTCOME MEASURE(S): The occurrence of LLCS after laparoscopic surgery for extensive endometriosis, in this case, and the prevention of subsequent LLCS after the application of a novel patient positioning method including the following steps: maximal avoidance of the lithotomy position, patient positioning in a modified supine position, mobilization of the legs of the patient in between different surgical phases, and application of intermittent compression stockings. RESULT(S): The prevalence of lower limb compartment syndrome has been reduced to 0 since the application of the new patient positioning method. CONCLUSION(S): Lower limb compartment syndrome can be prevented in patients undergoing long duration multidisciplinary laparoscopic resection of extensive endometriosis by a novel sequential positioning method of patients before and during surgery.

Anaesthetic issues in women undergoing gynaecological cytoreductive surgery.

PURPOSE OF REVIEW: Increasing numbers of women with ovarian cancer are undergoing cytoreductive surgery in reference centres. This review looks at this disease in these women and the different aspects of perioperative clinical management of these patients by the anaesthetic team: preoperative screening, anaesthetic techniques, fluid or blood management or both and prevention and treatment of important complications. RECENT FINDINGS: The outcome for women with ovarian cancer can be influenced not only by the timing of surgery or chemotherapy or both but also by anaesthetic technique, especially by combining general anaesthesia and central neural blockade, by a rational approach to perioperative fluid management and by administration of statins. SUMMARY: Anaesthesia is more than 'keeping asleep'. Anaesthesiologists have an enormous responsibility in the preoperative, peroperative, and postoperative period for patients undergoing gynaecological cytoreductive surgery.

Effects of adding small amounts of oxygen to a carbon dioxide-pneumoperitoneum of increasing pressure in rabbit ventilation models.

OBJECTIVE: To evaluate the metabolic consequences of the addition of oxygen to the CO(2)-pneumoperitoneum. DESIGN: Prospective randomized study in rabbits. After 30 minutes of ventilation pneumoperitoneum was maintained for 90 minutes with pure CO(2) or CO(2) with 2% or 6% of oxygen. The intraperitoneal pressure was increased from 10 to 15 and 20 mm Hg every 30 minutes. Ventilation rate was either fixed or a progressive hyperventilation. End points were changes in arterial blood gases (Pco(2), Po(2)), pH, acid-base balance (actual base excess [ABE], standard bicarbonate [SBC], standard base excess [SBE], hydrogen carbonate [HCO(3)(-)], concentration of total carbon dioxide [Tco(2)]); oxygen and oximetry (oxyhemoglobin [O(2)Hb], oxygen saturation [So(2)], reduced hemoglobin [RHb], total oxygen concentration [To(2)], and oxygen tension at half saturation assessing hemoglobin oxygen affinity [p50]); and lactate concentrations assayed every 15 minutes. SETTING: University research center. ANIMALS: Twenty-four adult female New Zealand white rabbits. INTERVENTION(S): Anesthesia, mechanical ventilation, and pneumoperitoneum. RESULT(S): The effects of CO(2)-pneumoperitoneum on all end points increased with the elevated intraperitoneal pressure and were more pronounced when ventilation was fixed. Changes were less when 2% or 6% of oxygen had been added to the CO(2)-pneumoperitoneum. With use of logistic regression, the addition of oxygen, intraperitoneal pressure, and ventilation were found to be independent variables affecting Pco(2), pH, ABE, SBE, HCO(3)(-), O(2)Hb, So(2), p50, and end-tidal CO(2). CONCLUSION(S): The metabolic consequences of the combined effect of increased intraperitoneal pressure and CO(2)-pneumoperitoneum were less when 2% to 6% of oxygen was added or when animals were hyperventilated. We suggest that metabolic and mesothelial hypoxemia caused by CO(2) absorption can be reduced by adding small amounts of oxygen and by hyperventilation.

Robotic retroperitoneal lower para-aortic lymphadenectomy in cervical carcinoma: first report on the technique used in 5 patients.

OBJECTIVE: Retroperitoneal para-aortic laparoscopic lymphadenectomy is a technically challenging operation. The robotic Da Vinci system might be valuable in this operation due to a steady three-dimensional visualization, instrumentation with articulating tips, and an adaptive downscaling of the surgeons movements (without tremor). To the best of our knowledge, this is the first report on robotic retroperitoneal para-aortic lymphadenectomy in patients with gynecologic cancer. METHOD AND RESULTS: We report on the technique and operative results of the robotic retroperitoneal lower para-aortic lymphadenectomy using the Da Vinci Surgical System. Five patients with cervical carcinoma stage IIb-IIb were included. Technically the procedure was easier to perform than with the classical retroperitoneal laparoscopic approach. However using the Da Vinci Surgical System it is important to tilt the patient slightly to the left to avoid collision between the left arm of the patient and the robotic arms, and to place the endoscopic robotic arm between the 2 arms used for dissection. Finally, we experienced that using a 30 degrees scope is advantageous for the dissection of the paracaval nodes. None of the patients had evidence of para-aortic metastases on preoperatively staging, including Positron Emission Tomography - Computed Tomography (PET-CT). One of the patients had positive para-aortic lymph nodes. CONCLUSION: Here we report on the surgical technique used in our first 5 patients undergoing retroperitoneal para-aortic lymphadenectomy using the robotic Da Vinci system. It is important to adapt the surgical technique using the Da Vinci Surgical System compared with the classical laparoscopic technique.

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.

Role of CO(2) pneumoperitoneum-induced acidosis in CO(2) pneumoperitoneum-enhanced adhesion formation in mice.

The effect of assisted ventilation and CO(2) pneumoperitoneum during laparoscopic surgery upon blood gases and adhesion formation were evaluated in mice. We confirmed that the CO(2) pneumoperitoneum induces acidosis and enhances adhesion formation, and an association between both effects was demonstrated, together with its modulation by the assisted ventilation.

Pathogenesis of CO(2) pneumoperitoneum-induced metabolic hypoxemia in a rabbit model.

STUDY OBJECTIVE: To investigate the effects of carbon dioxide (CO(2)) pneumoperitoneum-induced changes in blood gases, acid-base balance, and oxygen homeostasis in rabbits. DESIGN: Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING: University training and teaching center. SUBJECTS: Twenty-six adult female New Zealand white rabbits. INTERVENTION: Anesthesia and pneumoperitoneum. MEASUREMENTS AND MAIN RESULTS: In anesthetized rabbits arterial blood gases, acid-base balance, oxygenation values, and lactate concentrations were assayed during 2 hours. Spontaneous breathing, superficial and optimal ventilation without pneumoperitoneum, and with pneumoperitoneum at low (6 mm Hg) and higher (10 mm Hg) insufflation pressures were compared. The CO(2) pneumoperitoneum profoundly affected blood gases, acid-base balance, and oxygen homeostasis. Carboxemia with increasing end-tidal CO(2) and partial pressure of CO(2) (p <0.001), acidosis with decreasing pH (p <0.001), and base deficiency with decreasing actual base excess (p <0.001), standard base excess and standard bicarbonate and acid excess with increasing hydrogen bicarbonate (p <0.05 and <0.01) were found. Desaturation (p <0.01) with decreasing oxyhemoglobin p <0.05) and hemoglobin oxygen affinity (p <0.01) were also found. Carboxemia with acidosis was more pronounced with higher (p <0.01) than with lower (p >0.05) intraperitoneal pressures, and also with spontaneous breathing (p <0.05) and superficial ventilation (p <0.001) than with optimal ventilation, resulting in metabolic hypoxemia. CONCLUSION: In superficially ventilated and spontaneously breathing rabbits, CO(2) pneumoperitoneum profoundly affected blood gases, acid-base balance, and oxygen homeostasis, resulting in metabolic hypoxemia. With optimal ventilation and low intraperitoneal pressure carboxemia, respiratory acidosis, and changes in oxygen metabolism were minimal.

Reduction of CO(2)-pneumoperitoneum-induced metabolic hypoxaemia by the addition of small amounts of O(2) to the CO(2) in a rabbit ventilated model. A preliminary study.

BACKGROUND: CO(2)-pneumoperitoneum used in endoscopic surgery induces system effects by CO(2) absorption. This study investigated the effect of the addition of O(2) to CO(2)-pneumoperitoneum, upon CO(2) absorption. METHODS: The effect of a pneumoperitoneum using 100% CO(2) or 94% CO(2) + 6% O(2) upon arterial blood gases, acid base and O(2) homeostasis was evaluated. In series A suboptimal ventilation and a pneumoperitoneum pressure (PP) of 10 mmHg was used. In series B adequate ventilation and PP of 6 mmHg was used. RESULTS: CO(2)-pneumoperitoneum profoundly affected blood gases and acid base homeostasis i.e. increasing pCO(2), HCO(3)(P < 0.001) and lactate concentrations (P < 0.05) and decreasing pH, actual base excess and standard bicarbonate (P < 0.001), resulting in metabolic hypoxaemia with desaturation, lower pO(2) (P < 0.001) and O(2)Hb (P < 0.05). These effects were more pronounced with higher PP and suboptimal ventilation. CONCLUSION: CO(2)-pneumoperitoneum profoundly affected blood gases and acid base homeostasis resulting in metabolic hypoxaemia. The addition of 6% of O(2) to the CO(2)-pneumoperitoneum prevented these effects to a large extent. If these preliminary data are confirmed in the human, the addition of a few percent of O(2) to CO(2) could become important for endoscopic surgery of long duration, especially in obese patients with limited cardiorespiratory adaptation and steep Trendelenburg.

A comparison of neuromuscular effects, tracheal intubating conditions, and reversibility of rapacuronium versus mivacurium in female patients.

IMPLICATIONS: Rapacuronium is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocking drug. We evaluated the intubating conditions at maximum block after the administration of rapacuronium or mivacurium in female patients undergoing laparoscopy. We also evaluated the neostigmine-induced reversibility of neuromuscular block after this single dose of rapacuronium or mivacurium.