A Dedicated Acute Pain Service Is Associated With Reduced Postoperative Opioid Requirements in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The Acute Pain Service (APS) was initially introduced to optimize multimodal postoperative pain control. The aim of this study was to evaluate the association between the implementation of an APS and postoperative pain management and outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: In this propensity-matched retrospective cohort study, we performed a before-after study without a concurrent control group. Outcomes were compared among patients undergoing CRS-HIPEC when APS was implemented versus historical controls (non-APS). The primary objective was to determine if there was a decrease in median total opioid consumption during postoperative days 0-3 among patients managed by the APS. Secondary outcomes included opioid consumption on each postoperative day (0-6), time to ambulation, time to solid intake, and hospital length of stay. RESULTS: After exclusion, there were a total of 122 patients, of which 51 and 71 were in the APS and non-APS cohort, respectively. Between propensity-matched groups, the median (quartiles) total opioid consumption during postoperative days 0-3 was 27.5 mg intravenous morphine equivalents (MEQs) (7.6-106.3 mg MEQs) versus 144.0 mg MEQs (68.9-238.3 mg MEQs), respectively. The median difference was 80.8 mg MEQs (95% confidence interval, 46.1-124.0; P < .0001). There were statistically significant decreases in time to ambulation and time to solid diet intake in the APS cohort. CONCLUSIONS: After implementing the APS, CRS-HIPEC patients had decreased opioid consumption by >50%, as well as shorter time to ambulation and time to solid intake. Implementation of an APS may improve outcomes in CRS-HIPEC patients.

Exposing cells to H2O2: a quantitative comparison between continuous low-dose and one-time high-dose treatments.

Most studies investigating the influence of H2O2 on cells in culture apply nonphysiological concentrations over nonphysiological time periods (i.e., a one-time bolus that is metabolized in minutes). As an alternative, the glucose oxidase/catalase (GOX/CAT) system allows application of physiologically relevant H2O2 concentrations (300nM-10µM) over physiologically relevant time periods (up to 24h). Recent findings suggest that bolus and GOX/CAT treatments can lead to opposing cellular responses, thus warranting a quantitative comparison between the two approaches. First, we established a reaction-diffusion model that can predict the behavior of the GOX/CAT system with spatiotemporal resolution, thus aiding selection of optimal experimental conditions for its application. Measurements of H2O2 concentration in the cellular supernatant with the luminol/hypochlorite system were consistent with the predictions of the model. Second, we compared the impact of bolus and GOX/CAT treatments on cytosolic H2O2 levels over time. Intracellular H2O2 was monitored by the response of the thiol peroxidase Prx2 and the H2O2 sensor roGFP2-Orp1. We found that Prx2 rapidly and reversibly responds to submicromolar H2O2 levels and accurately reflects kinetic competition with cellular catalase. Our measurements reveal fundamental differences in the dynamic response of cellular H2O2 concentrations following either bolus or GOX/CAT treatments. Thus, different, or even opposing, biological outcomes from differing means of H2O2 delivery may be expected. Cellular responses induced by bolus treatment may not occur under GOX/CAT conditions, and vice versa.

St. John's wort extract LI160 for the treatment of depression with atypical features - a double-blind, randomized, and placebo-controlled trial.

Preliminary data suggest that hypericum extract LI160 is effective in atypical depression. Reported is the outcome of an 8-week double-blind, placebo-controlled, randomized trial of 600 mg LI160 vs. placebo in patients with vegetative features of atypical depression, i.e. hyperphagia or hypersomnia. One-hundred (100) patients with mild and 100 patients with moderate severity of a major depression according to ICD-10 were randomized. Patients needed to meet a score of 2 in at least one of the items 22-26 of the Hamilton-Depression-Rating-Scale (HAM-D) 28-item version and episode duration of at least 3 months. The primary outcome variable was the relative change of the HAM-D(17) from Baseline. Secondary outcome variables were the depression sub-score of the Patient Health Questionnaire (PHQ-9), the Clinical Global Impression (CGI), a patient's satisfaction scale, the Hamilton-Anxiety-Scale (HAM-A) and the sum score of atypical vegetative symptoms of the HAM-D(28). The percentage reduction of the HAM-D(17) for LI160 compared to placebo approached statistical significance (p=0.051) in the Full Analysis Set (FAS)-population. Using the conventional criterion of the absolute reduction of the HAM-D(17) significance was achieved (p<0.05). No significant benefit could be observed for the sum score of the atypical vegetative items of the HAM-D(28;) however, the sum score of the hypersomnia items (items 22-24) showed a significant superiority for LI160. The HAM-A, PHQ-9, and CGI-I scales demonstrated superiority of LI160 (p<0.01). Confining the analysis to moderately depressed patients, a highly significant benefit for the primary outcome variable was revealed. The study supports the beneficial effect of LI160 in depression with atypical features and the validity of the definition of atypical depression on the basis of reversed vegetative signs. Further, it identifies the PHQ-9 as a useful outcome variable in this population.

Hemodynamic management and outcome of patients treated for cerebral vasospasm with intraarterial nicardipine and/or milrinone.

BACKGROUND: Vasospasm is a potentially devastating complication after aneurysmal subarachnoid hemorrhage. Although endovascular treatment with intraarterial nicardipine and milrinone is an accepted clinical treatment strategy, there is little information either on hemodynamic management during treatment or on outcome and consequences of the hemodynamic management. We tested 2 hypotheses: (1) intraarterial administration of nicardipine and milrinone to treat cerebral vasospasm would require increased administration of vasoconstrictor to support arterial blood pressure at target levels; and (2) high-dose vasopressors administered to increase blood pressure in these patients would lead to systemic acidosis and end-organ ischemic damage. METHODS: We conducted a single-center, retrospective review of consecutive patients with clinically symptomatic vasospasm after aneurysmal subarachnoid hemorrhage that failed medical management with "triple H therapy" and subsequently received intraarterial nicardipine and/or milrinone between March 2005 and July 2007. RESULTS: Of 160 endovascular interventions in 73 patients (aged 52 +/- 10 years; 50 women), 96 received only nicardipine, 5 only milrinone, and 59 both drugs. General anesthesia with muscle relaxation was performed for 93% of procedures. During treatment, both the number and dose of vasopressors required to maintain arterial blood pressure at target levels increased; the median dose of phenylephrine increased from 200 (n = 121) to 325 microg/min (n = 122), norepinephrine increased from 12 (n = 60) to 24.5 microg/min (n = 87), and vasopressin infusions increased from 7 to 24. Nonetheless, arterial blood pressure decreased 13% during treatment. In >90% of procedures, the postprocedure angiogram showed improved vessel caliber. A single patient demonstrated troponin T increase; no patients had a decrease in renal function, bowel or peripheral ischemia, systemic acidosis, or acute stroke. Overall mortality was 11%. CONCLUSIONS: Intraarterial administration of nicardipine and/or milrinone requires use of vasopressors to maintain arterial blood pressure. Despite high doses of vasoconstrictors, treatment has low mortality, minimal end-organ ischemic damage or systemic acidosis, and results in improved caliber of cerebral vessels affected by vasospasm.