Real-world experience with neuromuscular blockade reversal.

Neuromuscular blocking agents are used in many surgical procedures and have enabled new surgical advances. The expanded landscape of neuromuscular blockade (NMB) reversal drugs allows for fast and complete NMB reversal and the reduction of postoperative complications from residual block. In the United States, neostigmine/glycopyrrolate and sugammadex are the primary agents for pharmacologic antagonism of neuromuscular blocking agents. Whereas neostigmine and an anticholinergic have been available for decades, sugammadex has only recently become available. We present real-world cases in a variety of surgical procedures and clinical settings in which the use of NMB reversal agents played a significant role in the patients' clinical outcome. Online access: http://courses.elseviercme.com/nmb/711.

Intravenous acetaminophen for pain after major orthopedic surgery: an expanded analysis.

BACKGROUND AND METHODS: From the time that Sinatra et al. (Anesthesiology. 2005;102:822) was published to FDA apaproval of intravenous (IV) acetaminophen, an expanded analysis of the original raw study data became necessary for the regulatory submission. The following analyses were conducted: (1) sum of pain intensity differences over 24 hours (SPID24) using currently accepted imputation methods to account for both missing data and the effects of rescue; (2) efficacy results after the first 6 hours; (3) effects of gender, race/ethnicity, age, weight, surgical site, ASA Class, and serotonin antagonists; and (4) a stepwise regression analysis of why adverse events of nausea and vomiting were numerically (although not statistically) higher in the IV acetaminophen group compared with placebo. RESULTS: Sum of pain intensity differences over 24 hours using a 0- to 100-mm visual analog scale was statistically significantly (P < 0.001) in favor of IV acetaminophen (n = 49) compared with placebo (n = 52). Time to rescue was found to be 3.9 and 2.1 hours, respectively, for total hip and knee arthroplasty compared with 0.8 hours for the placebo group. Rescue medication consumption, requests, and actual administration were all significantly lower in the IV acetaminophen group compared with placebo for each dosing interval, except in the 6- to 12-hours interval where a numerical trend was observed. Analysis of various subset variables demonstrated similar efficacy for each variable. A stepwise regression analysis demonstrated that AE reports of nausea and vomiting were most likely due to prerandomization events, particularly opioid consumption and presence of nausea prior to randomization. CONCLUSION: Repeated-dose 24-hours end points were found to be as robust as previously published results. IV acetaminophen efficacy and safety appeared to be unaffected by specific subset variables.▪

Role of intravenous acetaminophen in postoperative pain management.

SUMMARY The need to safely treat the postoperative pain of patients is apparent. Opioids, although effective, have multiple morbidities associated with their use. A multimodal approach to postoperative pain management can serve to minimize the undesirable effects of opioids. Intravenous acetaminophen (paracetamol) has recently become available in the USA where many practitioners are not familiar with this drug. This article reviews the history, pharmacology and clinical uses of intravenous acetaminophen in the treatment of perioperative pain.

A randomized, dose-finding, phase II study of the selective relaxant binding drug, Sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular block.

BACKGROUND: The reversal of a deep neuromuscular blockade remains a significant clinical problem. Sugammadex, a modified gamma-cyclodextrin, encapsulates steroidal neuromuscular blocking drugs, promoting their rapid dissociation from nicotinic receptors. Sugammadex is the first drug that acts as a selective relaxant binding agent. METHODS: We enrolled 50 patients into a Phase II dose-finding study of the efficacy and safety of sugammadex. Subjects, anesthetized with nitrous oxide and propofol, were randomized to one of two doses of rocuronium (0.6 or 1.2 mg/kg) and to one of five doses of sugammadex (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg). Neuromuscular monitoring was performed using the TOF Watch SX acceleromyograph. Recovery was defined as a train-of-four ratio > or =0.9. Sugammadex was administered during profound block when neuromuscular monitoring demonstrated a posttetanic count of one or two. RESULTS: Reversal of neuromuscular block was obtained after administration of sugammadex in all but the lowest dose groups (0.5-1.0 mg/kg) where several subjects could not be adequately reversed. At the 2 mg/kg dose all patients were reversed with sugammadex, but there was significant variability (1.8-15.2 min). Patient variability decreased and speed of recovery increased in a dose-dependent manner. At the highest dose (8 mg/kg), mean recovery time was 1.2 min (range 0.8-2.1 min). No serious adverse events were reported during this trial. CONCLUSIONS: Sugammadex was well tolerated and effective in rapidly reversing profound rocuronium-induced neuromuscular block. The mean time to recovery decreased with increasing doses. Profound rocuronium-induced neuromuscular block can be reversed successfully with sugammadex at doses >/=2 mg/kg.

Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery.

BACKGROUND: Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr. METHODS: After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing. RESULTS: One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively. CONCLUSION: Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.

Significant hyperkalemia after discontinuation of an insulin pump.

Patients with diabetes and insulin pumps may need their insulin therapy modified during surgery. Often, this is done with blood glucose as the end point. Changing insulin therapy can also have profound effects on potassium homeostasis in certain patients. This case demonstrates that changes in insulin therapy warrant not only close monitoring of blood glucose, but also of serum potassium. This patient's comorbidities and treatments that could alter potassium homeostasis are also reviewed.