[Pathophysiology of intracranial injuries]. / Pathophysiologie intrakranieller Verletzungen.

Traumatic brain injury (TBI) constitutes a heterogeneous condition that affects the most complex organ of the human body. It is commonly classified by its location as focal injury (e.g. epidural hematoma) and diffuse injury (e.g. diffuse axonal shearing injury) as well as by primary and secondary tissue injury. Accordingly, direct mechanical force causes the primary insult. The tissue damage occurring afterwards is subsumed under the term secondary brain damage. Some of these processes are overlapping and include in the early phase local cerebral ischemia resulting in excitotoxicity, which together with the triggered neuroinflammatory cascade causes the formation of cerebral edema and ultimately increased intracranial pressure once the intracranial compliance is exhausted. In survivors the long-term sequelae of the late stage include seizures caused by synaptic reorganization (incidence depending on the severity of TBI), persistent neuroinflammation promoting further neurodegeneration and increased risk for Alzheimer's disease probably because of TBI-related protein misfolding (tauopathy). Acute phase biomarkers of TBI should ideally originate from the injured brain. They should help distinguish disease severity and predict morbidity and mortality; however, the most commonly used biomarkers (S-100ß and neurone-specific enolase) show a low specificity. In theory their successors (i. e. GFAP, pNF-H) seem more specific; however, these "new kids on the block" still need to be thoroughly investigated in large scale studies.

The effect of lipid emulsion on depth of anaesthesia following thiopental administration to rabbits.

Intravenous lipid emulsion has proven benefit in lipophilic drug-induced cardiotoxicity. Its effect in reversal of central nervous system depression secondary to overdose with lipophilic psychotropic agents remains uncertain. Twenty adult New Zealand White rabbits were anaesthetised with 20 mg.kg(-1) thiopental and randomised to receive either 4 ml.kg(-1) saline 0.9% or 4 ml.kg(-1) lipid emulsion 20% immediately afterwards. Depth of anaesthesia was monitored using bispectral index (BIS) at 1-min intervals. Duration of anaesthesia was measured as time to regain the righting reflex (ability of the animal to right spontaneously from dorsal recumbency to sternal recumbency). The BIS was greater in the control group (p = 0.011). The greatest BIS differential was observed immediately following treatment (mean (SD) BIS 75.0 (9.5) for saline vs 58.6 (10.4) for lipid, 95% CI 5.75-27.1; p < 0.001). No difference was observed in duration of anaesthesia (mean (SD) 15.5 (0.8) min for saline vs 15.6 (0.7) min for lipid, p = 0.86). Lipid emulsion administration may serve to increase central nervous system depression in the early phase of lipophilic toxin distribution.

Effect of hypertonic saline on electrocardiography QRS duration in rabbit model of bupivacaine toxicity resuscitated by intravenous lipid.

Intravenous lipid emulsion is established therapy for bupivacaine induced cardiotoxicity. The benefit of combined hypertonic saline and lipid treatment is unexplored. In this experiment, sedated rabbits were resuscitated from bupivacaine-induced asystole with intravenous lipid according to the Association of Anaesthetists of Great Britain and Ireland's guideline, or by identical lipid dosing with hypertonic saline: 6 mEq x kg(-1) 21% sodium chloride. Early electrocardiography QRS prolongation was less with lipid plus hypertonic saline (mean (SD) QRS 0.19 (0.07) s lipid only vs 0.09 (0.01) s lipid plus hypertonic saline; p = 0.003) at 9 min though not different from the lipid only group at 20 min. No difference was observed in rates of circulatory return (7/10 lipid only and 9/10 lipid plus hypertonic saline; p = 0.58) or survival (5/10 lipid only and 6/10 lipid plus hypertonic saline; p = 1.00). Some benefit to cardiac conduction may be afforded by hypertonic saline co-administered with lipid emulsion in bupivacaine-induced cardiotoxicity.

Evaluation of stroke volume variation obtained by arterial pulse contour analysis to predict fluid responsiveness intraoperatively.

BACKGROUND: Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. METHODS: Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to <350 ms. Patients were connected to a monitoring device, obtaining SVV by APCO. Haemodynamic variables were recorded before and after fluid bolus application. Fluid responsiveness was defined as an increase in stroke volume index >10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. RESULTS: Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). CONCLUSIONS: This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.

Acute pulmonary hypertension and right ventricular failure in adult respiratory distress syndrome.

The severity of acute pulmonary hypertension (APHT) in acute respiratory distress syndrome was examined in 20 patients. All patients had significant APHT (mean pressure 40.6 +/- 6.3 mmHg) on admission to the intensive care unit. There was evidence of right ventricular (RV) failure, with a right ventricular stroke work index (RVSWI) of 9.20 +/- 3.3 g.m/m2 and a central venous pressure of 18.0 +/- 4.0 mmHg. The RV afterload, i.e. pulmonary artery elastance (Ea = stroke volume/peak pulmonary artery pressure), was raised. Stroke volume could not be predicted from Ea or RVSWI alone, but regression analysis indicated that the ratio of RVSWI/Ea (i.e. ventriculo-arterial coupling) could account for 88% of the stroke volume.

Nitric oxide has little effect on acute pulmonary hypertension and right ventricular function during acute respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of nitric oxide (NO) on acute pulmonary hypertension and right ventricular function in patients with acute respiratory distress syndrome. DESIGN: A prospective clinical study. PATIENTS: Ten patients in the respiratory and surgical intensive care units were used. They met the criteria for acute respiratory distress syndrome and were significantly hypoxic. They were all ventilator-dependent at the time of the study. INTERVENTION: NO was delivered to the patients in 5, 10, 20 and 30 ppm doses for 30 minutes at each concentration. The dosing was not randomised. MEASUREMENTS AND RESULTS: The general and central haemodynamics were measured. Right ventricular function and interaction with the pulmonary artery impedance (Ea) were quantified with the ratio of right ventricular stroke work index/Ea. NO did not decrease the raised pulmonary artery pressure found in all of the patients. Right ventricular coupling to the circulation did not improve during the administration of NO. CONCLUSION: NO did not relieve the acute pulmonary artery hypertension associated with acute respiratory distress syndrome. As a consequence of this, right ventricular function failed to improve during the administration of NO.