Neil W. Brister

Efficacy, Safety, and Pharmacokinetics of Sugammadex for the Reversal of Rocuronium-induced Neuromuscular Blockade in Elderly Patients

Background:The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18–64 yr) versus elderly adult (aged 65 yr or older) patients. Methods:This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1–3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated. Results:Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18–64 yr (adult), 62 were aged 65–74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0–2.6) min (adults) to 2.9 (2.7–3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients. Conclusion:Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.

Clevidipine in adult cardiac surgical patients: A dose-finding study

Background Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. Methods Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration–response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. Results There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 &mgr;g · kg−1 · min−1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 &mgr;g/l and for a 20% or greater decrease in mean arterial pressure was 26.3 &mgr;g/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. Conclusion Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.

Anesthetic Considerations in Candidates for Lung Volume Reduction Surgery

The administration of anesthesia to patients undergoing lung volume reduction surgery (LVRS) requires a complete understanding of the pathophysiology of severe chronic obstructive pulmonary disease, the planned surgical procedure, and the anticipated postoperative course for this group of patients. Risk factors and associated morbidity and mortality are discussed within the context of patients with obstructive pulmonary disease in the National Emphysema Treatment Trial having surgical procedures. Preoperative evaluation and the anesthetic techniques used for patients undergoing LVRS are reviewed, as are monitoring requirements. Intraoperative events, including induction of anesthesia, lung isolation, management of fluid requirements, and options for ventilatory support are discussed. Possible intraanesthetic complications are also reviewed, as is the optimal management of such problems, should they occur. To minimize the potential for a surgical air leak in the postoperative period, positive-pressure ventilation must cease at the conclusion of the procedure. An awake, comfortable, extubated patient, capable of spontaneous ventilation, is only possible if there is careful attention to pain control. The thoracic epidural is the most common pain control method used with patients undergoing LVRS procedures; however, other alternative methods are reviewed and discussed.

Sequestration of vecuronium bromide during extremity surgery involving use of a pneumatic tourniquet

Background: We hypothesized that sequestration of a neuromuscular blocking agent could occur during surgery involving use of an extremity tourniquet and cause changes in neuromuscular function after tourniquet release.

The Use of Somatosensory Evoked Potentials to Determine the Relationship Between Intraoperative Arterial Blood Pressure and Intraoperative Upper Extremity Position-Related Neurapraxia in the Prone Surrender Position During Spine Surgery: A Retrospective Analysis.

BACKGROUND:Peripheral nerve injury is a significant perioperative problem. Intraoperative position-related neurapraxia may indicate impending peripheral nerve injury and can be detected by changes in somatosensory evoked potentials (SSEP). The purpose of this retrospective analysis of spine surgeries performed under general anesthesia with SSEP monitoring was to determine the relationship between intraoperative mean arterial blood pressure (MAP) and intraoperative upper extremity position–related neurapraxia in the prone surrender (superman) position. METHODS:We reviewed a computerized database of spine surgeries performed on adult patients in the prone surrender position. The authors reviewed intraoperative SSEP monitoring reports to identify the patients who developed intraoperative upper extremity position–related neurapraxia (case group) and patients who did not (control group). Propensity matching was performed to derive 2 demographically matched groups. Preoperative and intraoperative variables were included in the univariate Cox regression analysis of risk factors associated with neurapraxia. Multivariate Cox regression models were used to identify the independent risk factors. RESULTS:One hundred fifty-two patients were included in the analysis. The case group included 32 patients, whereas the control group included 120 matched patients. Intraoperative MAP <55 mm Hg for a total duration of ≥5 minutes was an independent risk factor associated with a greater incidence of upper extremity position–related neurapraxia compared with a duration of <5 minutes with MAP <55 mm Hg (hazard ratio, 3.43; confidence interval, 1.445–8.148; P = 0.0052). Intraoperative MAP >80 mm Hg for a total duration of >55 minutes was an independent predictor associated with a lower incidence of neurapraxia compared with a total duration ⩽55 minutes (hazard ratio, 0.341; confidence interval, 0.163–0.717; P = 0.0045). CONCLUSIONS:In this study, we identified the changes in intraoperative MAP as independent predictors associated with upper extremity position–related neurapraxia in the prone surrender position under general anesthesia.

ISRADIPINE FOR TREATMENT OF ACUTE HYPERTENSION AFTER MYOCARDIAL REVASCULARIZATION

Objective.To evaluate the efficacy and duration of action of iv isradipine in the control of postoperative hypertension immediately after myocardial revascularization. Design.Prospective, phase 2 trial. Setting.Surgical ICU, university hospital. Patients.Twenty-one (15 male, six female) patients, ages 49 to 75 yr (mean 65 ± 5), undergoing elective myocardial revascularization. Interventions.Twenty-one patients with postoperative hypertension after coronary artery bypass graft surgery received iv isradipine, a new dihydropyridine calcium-channel antagonist. Mean duration of the isradipine infusion was 96.9 ± 29 min. Mean dose of isradipine, indexed to weight, was 16.63 ± 6.66 μg/kg (n = 20). Measurements and Main Results.Twenty of the 21 patients achieved satisfactory BP control. The reduction in mean arterial pressure (MAP), first noted at the 15-min point, was maximal at 1 hr when MAP decreased from 102 ± 9 mm Hg baseline to 81 ± 5 mm Hg (p < .01), accompanied by a significant (p < .01) decrease in systemic vascular resistance from 1753 ± 339 baseline to 1180 ± 229 dyne-sec/cm5. The CVP, pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure did not change significantly. Heart rate and cardiac index increased; however, stroke volume index did not change. Conclusions.Isradipine is an acceptable agent for the treatment of hypertension in this setting. (Crit Care Med 1991; 19:334)

Intravenous vitamin K1 prior to orthotopic heart transplantation : effects in vivo and in vitro

Background: Vitamin Kj is used to reverse warfarins anticoagulant action. It is unclear whether intravenous vitamin K1 is safe or efficacious prior to urgent cardiac surgery.

Pharmacologic Hemodynamic Therapy of Shock

Know the indications and contraindications for each medication. Know the clinical hemodynamic effects of each medication. Know the potential complications associated with each medication. Know the use of these agents in specific shock states.