Clinical validation of an adapted Eleveld Model for high-dose propofol treatments for depression.

Repeated administration of high doses of propofol to patients with treatment-resistant depression (TRD) has been shown to produce antidepressant effects in small clinical trials. These effects can be elicited when the patient's EEG burst-suppression ratio (BSR) is maintained at 70-90% for 15 min in repeated treatments. This deep anesthesia domain lies beyond the range of current propofol pharmacokinetic/pharmacodynamic (PK/PD) models. In this study, we adapt the Eleveld model for use at deep anesthesia levels with a BSR endpoint, with the goal of aiding the estimation of the dosage of propofol needed to achieve 70-90% BSR for 15 min. We test the ability of the adapted model to predict BSR for these treatments. Twenty participants underwent 6-9 treatments of high doses of propofol (5-9 of which were included in this analysis) for a total of 115 treatments. To adapt the Eleveld model for this endpoint, we optimized the model parameters Ke0, γ and Ce50. These parameters were then used in the adapted model to estimate second-by-second BSR for each treatment. Estimated BSR was compared with observed BSR for each treatment of each participant. Median absolute performance error (MdAPE) between the estimated and observed BSR (25th-75th percentile) was 6.63 (3.79-12.96) % points and 8.51 (4.32-16.74) % between the estimated and observed treatment duration. This predictive performance is statistically significantly better at predicting BSR compared with the standard Eleveld model at deep anesthesia levels. Our adapted Eleveld model provides a useful tool to aid dosing propofol for high-dose anesthetic treatments for depression.

Leukocyte Gene Expression in Patients with Medication Refractory Depression before and after Treatment with ECT or Isoflurane Anesthesia: A Pilot Study.

Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia (ISO). Methods. In a substudy of a nonrandomized open-label trial comparing effects of ECT to ISO therapy, blood samples were obtained before and after treatment from 22 patients with refractory depression, and leukocyte mRNA was assessed by quantitative PCR. Patients' mRNAs were also compared to 17 healthy controls. Results. Relative to controls, patients before treatment showed significantly higher IL10 and DBI and lower ADRA2A and ASIC3 mRNA (P < 0.025). Both ECT and ISO induced significant decreases after treatment in 4 genes: IL10, NR3C1, DRD4, and Sult1A1. After treatment, patients' DBI, ASIC3, and ADRA2A mRNA remained dysregulated. Conclusion. Significant differences from controls and/or significant changes after ECT or ISO treatment were observed for 7 of the 9 mRNAs studied. Decreased expression of 4 genes after effective treatment with either ECT or ISO suggests possible overlap of underlying mechanisms. Three genes showing dysregulation before and after treatment may be trait-like biomarkers of medication refractory depression. Gene expression for these patients has the potential to facilitate diagnosis, clarify pathophysiology, and identify potential biomarkers for treatment effects.

Factors associated with the occurrence of cardiac arrest during hospitalization for acute myocardial infarction in the second national registry of myocardial infarction in the US.

Cardiac arrest can occur as a complication of acute myocardial infarction (AMI). To date, few studies have described factors associated with cardiac arrest occurrence and survival during hospitalization for treatment of AMI. We used data from a large national registry of hospitalized AMI patients to identify these factors. Data were collected from 1073 participating institutions, representing 14.4% of US hospitals. Hospital site coordinators conducted periodic chart reviews for AMI patients and data were submitted to an independent center for periodic review. Univariate analysis and multivariate logistic regression were used to identify factors associated with cardiac arrest. We found that cardiac arrest occurred in 4.8% (14,725/305,812) of hospitalized AMI patients. The survival rate to hospital discharge for these individuals was 29.4%. Sustained ventricular tachycardia or fibrillation (VT/VF) was present in 34.7% and was associated with a higher rate of survival to hospital discharge compared to cardiac arrest patients without a ventricular tachyarrhythmia (47.5 vs. 19.8%, P < 0.00001). Hypotension (initial systolic BP < 90 mmHg), q-wave AMI, old age, heart failure and initial heart rate abnormalities (bradycardia or tachycardia) were associated with a higher prevalence of cardiac arrest. A higher percentage of women compared to men experienced cardiac arrest (6.0 vs. 4.41%, P < 0.0001). Cardiac arrest prevalence was lower in patients with inferior wall infarction than in other types of ST-elevation infarction. Use of reperfusion therapy (PTCA or tPA) was associated with improved survival compared to hospitalized AMI patients who did not receive such therapy.

Intrathoracic stomach presenting as acute tension gastrothorax.

Total intrathoracic stomach creating pulmonary and hemodynamic compromise is a rare life-threatening complication in patients with hiatal hernia. The presentation and clinical course of this condition are discussed. Physicians should consider this entity in patients presenting with apparent tension pneumothorax without history or other evidence of trauma or positive pressure ventilation who do not respond to standard interventions.

Noninvasive cerebral cooling in a swine model of cardiac arrest.

OBJECTIVE: Mild cerebral hypothermia improves neurologic outcome in animals resuscitated from cardiac arrest. This study examined whether one practical external cooling method, i.e., local application of ice to the heads and necks of swine, during resuscitation induces cerebral cooling. METHODS: Local external cerebral cooling was examined in a prospective laboratory investigation using 24 female swine in a model of cardiac arrest. The swine were randomized into hypothermia and normothermia groups. Intracerebral temperature was measured in the parietal cortex. Eight minutes after induction of ventricular fibrillation, chest compressions and mechanical ventilation were initiated. The hypothermia group was treated with 1,500 mL of ice in plastic bags applied to the head and neck, while the normothermia group received no extra interventions. Data were analyzed using repeated-measures ANOVA. RESULTS: In the normothermia group, there was no significant change in nasopharyngeal (-0.8 +/- 0.6 degree C), intracerebral (-0.6 +/- 0.8 degree C), or esophageal (-0.2 +/- 0.6 degree C) temperatures during 20 minutes of resuscitation. However, in the hypothermia group, application of ice during resuscitation significantly reduced nasopharyngeal (-2.9 +/- 1.4 degrees C), intracerebral (-2.1 +/- 0.6 degrees C), and esophageal (-1.4 +/- 0.8 degrees C) temperatures. CONCLUSIONS: External application of ice packs during resuscitation effectively reduced intracerebral temperatures in swine by an amount that improved neurologic outcomes in previous large animal studies. These data suggest that clinically significant cerebral cooling could be accomplished with a noninvasive, inexpensive, and universally available intervention. Further studies are required to assess the clinical feasibility and therapeutic efficacy of this intervention.