Efficacy of Malignant Hyperthermia Association of the United States-Recommended Methods of Preparation for Malignant Hyperthermia-Susceptible Patients Using Dräger Zeus Anesthesia Workstations and Associated Costs.

BACKGROUND: The objective of this study was to assess the efficacy and cost of Malignant Hyperthermia Association of the United States-recommended methods for preparing Dräger Zeus anesthesia workstations (AWSs) for the malignant hyperthermia-susceptible patient. METHODS: We studied washout profiles of sevoflurane, isoflurane, and desflurane in 3 Zeus AWS following 3 preparation methods. AWS was primed with 1.2 minimum alveolar concentration anesthetic for 2 hours using 2 L/min fresh gas flow, 500 mL tidal volume, and 12/min respiratory rate. Two phases of washout were performed: high flow (10 L/min) until anesthetic concentration was <5 parts per million (ppm) for 20 minutes and then low flow (3 L/min) for 20 minutes to identify the rebound effect. Preparation methods are as follows: method 1 (M1), changing disposables (breathing circuit, soda lime, CO2 line, and water traps); method 2 (M2), M1 plus replacing the breathing system with an autoclaved one; and method 3 (M3), M1 plus mounting 2 activated charcoal filters on respiratory limbs. Primary outcomes are as follows: time to obtain anesthetic concentration <5 ppm in the high-flow phase, peak anesthetic concentrations in the low-flow phase, and for M3 only, peak anesthetic concentration after 70 minutes of low-flow phase, when activated charcoal filters are removed. Secondary outcomes are as follows: cost analysis of time and resources to obtain anesthetic concentration <5 ppm in each method and a vapor-free Zeus AWS. Sensitivity analyses were performed using alternative assumptions regarding the costs and the malignant hyperthermia-susceptible caseload per year. RESULTS: Primary outcomes were as follows: M3 instantaneously decreased anesthetic concentration to <1 ppm with minimal impact of low-flow phase. M1 (median, 88 minutes; 95% confidence interval [CI], 69-112 minutes) was greater than M2 (median, 11 minutes; 95% CI, 9-15 minutes). Means of peak rebound anesthetic concentrations in M1, M2, and M3 were 15, 6, and 1 ppm, respectively (P < .001). Anesthetic concentration increased 33-fold (95% CI, 21-50) after removing charcoal filters (from 0.7 to 20 ppm). The choice of anesthetic agents did not impact the results. Secondary outcomes were as follows: M3 was the lowest cost when the cost of lost operating room (OR) time due to washout was included, and M1 was the lowest cost when it was not included. When the cost of lost OR time due to washout was considered the estimated cost/case of M3 was US $360 (M1, US $2670; M2, US $969; and a "vapor-free" Zeus AWS was US $930). The OR time and equipment costs represent the largest differentiators among the methods. CONCLUSIONS: Institutions in which demand for OR time has exceeded capacity should consider M3, and institutions with surplus OR capacity should consider M1.

Diagnostic Accuracy of Neuromonitoring for Identification of New Neurologic Deficits in Pediatric Spinal Fusion Surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) modalities, transcranial motor-evoked potentials (TcMEPs), and somatosensory-evoked potentials (SSEPs) are accepted methods to identify impending spinal cord injury during spinal fusion surgery. Debate exists over sensitivity and specificity of these modalities. Our purpose was to measure the incidence of new neurologic deficits (NNDs) and estimate sensitivity and specificity of IONM modalities. METHODS: Institutional Ethics Board approval was obtained to review charts of patients younger than 22 years undergoing scoliosis surgery from 2007 to 2014 retrospectively. The definition of true-positive patients included two subgroups: (1) patients with an IONM alert, which did not resolve despite the interventions and had a NND postoperatively; or (2) patients with an IONM alert triggering interventions and the alert resolved with no NND postoperatively. Subgroup 2 of the definition is debatable; thus, we performed a multiple sensitivity analysis with three assumptions. Assumption 1: without interventions, all such patients would have experienced NNDs (assumption used in previous studies); Assumption 2: without intervention, half of these patients would have experienced NNDs; Assumption 3: without intervention, none of these of patients would have experienced NNDs. RESULTS: We included 296 patients. Patients with incomplete charts (n = 3), no IONM monitoring (n = 11), and inadequate baseline IONM (n = 7) were excluded. The incidence of NND was 3.7% (95% confidence interval, 2.1%-6.5%). Successful IONM in at least one modality was obtained in 275 patients (92.9%), of whom 268 (97.5%) and 259 (94.2%) had successful baseline TcMEP or SSEP signals, respectively. Fifty-one (17%) patients had IONM alerts, 41 were only TcMEP, 5 were only SSEP, and 5 were in both modalities. After interventions, 42 (82%) patients recovered, 41 had no NND (true-positive under Assumption (1), but one developed a NND (false-negative). Of the 9 patients with no alert recovery, 6 had a NND (true-positive) and 3 did not (false-positives). Of the remaining 224 patients with no alerts, 221 had no NND (true-negatives) and 3 did (false-negatives). Sensitivity was estimated to be 93.5%, 92.2%, and 46.7% for TcMEPs, combination (either TcMEPs or SSEPs), and SSEPs, respectively. Multiple sensitivity analysis demonstrated that sensitivity and specificity vary markedly with different assumptions. CONCLUSION: TcMEPs are more sensitive than SSEP at detecting an impending NND. IONM modalities are highly specific. Both sensitivity and specificity are impacted substantially by assumptions of the impact of interventions on alerts and NND. Properly designed, controlled, multicenter studies are required to establish diagnostic accuracy of IONM in scoliosis surgery.

The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha 2-adrenoceptors.

Recent demonstrations of the anticonvulsant properties of agmatine suggest it may be considered as a potential adjunct for protection against seizure. We investigated the possibility of an additive anticonvulsant effect between low doses of agmatine and morphine. The thresholds for the clonic seizures induced by the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist, pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1-3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threshold. Pretreatment with a per se non-effective dose of agmatine (1mg/kg) potentiated the anticonvulsant effect of morphine. The combination of subeffective doses of agmatine and morphine led to potent anticonvulsant effects. The pro-convulsant effect of morphine was attenuated by agmatine. Yohimbine with a dose (1mg/kg) incapable of affecting seizure threshold reversed the effect of agmatine on both anticonvulsant and pro-convulsant effects of morphine. These results suggest that agmatine potentiates the anticonvulsant effect of morphine and alpha 2-adrenoceptors may be involved in this effect.

Obstructive cholestasis alters intestinal transit in mice: role of opioid system.

Acute cholestasis is associated with increased activity of the endogenous opioid system. It is also known that opioid receptor agonists like morphine decrease the intestinal transit. The purpose of the present study was to investigate the effect of cholestasis on the small intestine transit and the possible involvement of opioid system in this phenomenon in mice. Cholestasis was induced by bile duct-ligation and intestinal transit was measured with charcoal meal and calculation of percent of transit through small intestine. The effect of chronic administration of naltrexone and acute pretreatment with morphine on intestinal transit was evaluated in bile duct-ligated (BDL) as well as unoperated (CTL) and sham-operated (SHAM) animals. The plasma alkaline phosphatase and alanine aminotransferase activities were also measured. A significant decrease in small intestine transit (%transit) was observed in BDL mice compared to SHAM animals, which was prominent even after 24 h of cholestasis. Chronic pretreatment with an opioid receptor antagonist, naltrexone, (10 mg/kg, i.p for 2, 4 or 6 days) completely restored the cholestasis-induced decrease in %transit to that of control animals. Although the acute administration of morphine (2 mg/kg, s.c.) 20 min before charcoal feeding caused a significant decrease in the intestinal transit of CTL and SHAM animals, it did not decrease the %transit of BDL animals on the day 5 after operation. Our findings show that acute cholestasis is associated with a prominent decrease in small intestine transit in mice and opioid receptors maybe involved in this phenomenon.