Efficacy of hydrocortisone in preventing posttraumatic stress disorder following critical illness and major surgery.

Like other humans exposed to extreme trauma, patients who have been treated in an intensive care unit (ICU) often report traumatic memories. Extremely traumatic memories from the ICU in some of these patients are associated with the development of posttraumatic stress disorder (PTSD), which results in significant impairments in health-related quality of life (HRQL) outcomes of ICU therapy. Severely ill patients in the ICU often show insufficient endogenous glucocorticoid signaling, which has recently been termed critical illness-related corticosteroid insufficiency (CIRCI). We performed several controlled trials in ICU patients with suspected CIRCI from septic shock or cardiac surgery, which indicated that the administration of glucocorticoids (stress doses of hydrocortisone) during ICU treatment results in a significant reduction of PTSD symptoms in long-term survivors as well as improvements in HRQL outcomes. Stress doses of hydrocortisone could help to surmount impaired glucocorticoid signaling from CIRCI during critical illness resulting in a downregulation of the stress response as well as inhibition of traumatic memory retrieval and facilitated extinction of aversive information.

Comparison of systemic and renal effects of dopexamine and dopamine in norepinephrine-treated septic shock.

OBJECTIVES: Vasopressor-induced vasoconstriction may compromise renal and splanchnic blood flow in patients with septic shock, resulting in secondary organ failures. The authors compared the effects of the vasodilatatory agent dopexamine against renal-dose dopamine and placebo in patients with norepinephrine therapy and septic shock, using 24-hour serum creatinine clearance (C(crea)) as a major endpoint. The primary hypothesis to be tested was that dopexamine is more effective than dopamine and that dopamine shows better effects than placebo regarding organ failures and C(crea). DESIGN: A prospective, randomized, controlled, double-blinded study. SETTING: Intensive care unit in a tertiary care university hospital. PARTICIPANTS: Sixty-one patients with septic shock defined according to established criteria. INTERVENTIONS: Patients received either dopexamine (2 microg/kg/min, n = 20), dopamine (3 microg/kg/min, n = 21), or placebo (n = 20). RESULTS: The trial groups were similar in terms of baseline characteristics. The authors found no significant differences among the dopexamine, dopamine, and placebo groups with regard to a comprehensive number of renal function parameters including C(crea) and organ-failure scores. There was a significant increase in heart rate after dopexamine infusion; other hemodynamic parameters remained unchanged in the dopexamine group. In a post hoc analysis that included only patients with renal impairment at study inclusion (n = 28), patients who received dopamine showed significant improvements in C(crea) when compared with placebo. Dopexamine was not effective in this subgroup. CONCLUSIONS: Dopexamine is no more effective than dopamine or placebo regarding renal function in patients with septic shock requiring norepinephrine. Both therapies do not influence organ-failure scores.

Effects of general anesthesia on anandamide blood levels in humans.

BACKGROUND: The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Endocannabinoids play an important role in the physiologic control of sleep, pain processing, and emesis. The authors therefore investigated the effects of general anesthesia on the endocannabinoid system in humans. METHODS: The authors measured whole blood levels of anandamide in 12 patients after induction of general anesthesia with etomidate (an agent shown to have no effect on anandamide levels) and maintenance of anesthesia with the volatile agent sevoflurane as well as in 12 patients undergoing total intravenous anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the mouse brain. Anandamide levels were measured using high-performance liquid chromatography-tandem mass spectrometry at four time points (before and at 10, 20, 30, and 40 min after induction of anesthesia). RESULTS: Patients of the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min after induction, whereas anandamide levels in patients of the propofol group remained unchanged (type III sum of squares = 1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance). CONCLUSION: General anesthesia influences the endocannabinoid system in a drug-dependent way, which may explain side effects of general anesthetics such as psychomimetic and antiemetic properties of propofol and the high incidence of postoperative nausea and vomiting after volatile anesthetics. These findings suggest new targets for anesthetic drug development.

Effect of high altitude and exercise on microvascular parameters in acclimatized subjects.

The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface shear forces.