Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine.

OBJECTIVE: To assess the effects of dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients. DESIGN: A prospective, controlled trial. SETTING: A ten-bed intensive care unit (ICU) in a university hospital. PATIENTS: Twelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion. INTERVENTIONS: Infusion of increasing dosages of dopexamine (0.5, 1.0, 2.0, and 4.0 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow. Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption (VO2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients. CONCLUSIONS: In hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion.

What is new in asthma: new dry powder inhalers.

Asthma affects an estimated 4.8 million children. The pressurized metered-dose inhaler (pMDI), despite problems associated with its use and concern that most of these inhalers contain ozone-damaging chlorofluorocarbons (CFCs), is currently the device most frequently used to deliver inhaled medication. Concerns regarding pMDIs that contain CFCs have led to further development of alternative delivery devices, including CFC-free pMDIs, breath-actuated devices, and dry powder inhalers (DPIs). Advantages and disadvantages of these devices are discussed briefly, with emphasis on the new DPIs. A brief overview of their safety, efficacy, and acceptance by patients is presented. DPIs have the potential to become important devices for administration of inhaled medication in pediatric asthma management.

Epinephrine impairs splanchnic perfusion in septic shock.

OBJECTIVE: To assess the effects of epinephrine on splanchnic perfusion and splanchnic oxygen uptake in patients with septic shock. DESIGN: Prospective, controlled trial. SETTING: University hospital intensive care unit (ICU). PATIENTS: Eight patients with septic shock, according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, requiring treatment with vasopressors. INTERVENTIONS: We compared in crossover design a 2-hr infusion of epinephrine with dobutamine plus norepinephrine in eight ICU patients with septic shock. Systemic and splanchnic hemodynamics and oxygen transport were measured before and during treatment with epinephrine. MEASUREMENTS AND MAIN RESULTS: There was essentially no effect of epinephrine on the global parameters, except for increased lactate concentrations. There were marked effects on the regional variables; epinephrine caused lower splanchnic flow and oxygen uptake, lower mucosal pH, and higher hepatic vein lactate. CONCLUSION: We conclude that undesirable splanchnic effects on patients in whom that region is particularly fragile should be considered when using epinephrine for septic shock treatment.

The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock.

OBJECTIVE: To assess the effects of low-dose dopamine on splanchnic blood flow and splanchnic oxygen uptake in patients with septic shock. DESIGN: Prospective, controlled trial. SETTING: University hospital intensive care unit. PATIENTS: 11 patients with septic shock, diagnosed according the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference, who required treatment with norepinephrine. MEASUREMENTS AND MAIN RESULTS: Systemic and splanchnic hemodynamics and oxygen transport were measured before and during addition of low-dose dopamine (3 micrograms/kg per min). Low-dose dopamine and a marked effect on total body hemodynamics and oxygen transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57. In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption. In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did not appear to change splanchnic blood flow. CONCLUSION: Low-dose dopamine has a potential beneficial effect on splanchnic blood flow and oxygen consumption in patients with septic shock, provided the fractional splanchnic flow is not already high before treatment.

Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis.

OBJECTIVE: To assess global and splanchnic blood flow and oxygen transport in patients with sepsis with and without norepinephrine treatment. DESIGN: Prospective, clinical study. SETTING: University hospital intensive care unit. PATIENTS: A convenience sample of 15 septic shock patients treated with norepinephrine and 13 patients with severe sepsis who did not receive norepinephrine. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups in global haemodynamics and oxygen transport. Splanchnic blood flow and oxygen delivery (splanchnic DO2 303 +/- 43 ml/min per m2) and consumption (splanchnic VO2 100 +/- 13 ml/min per m2) were much higher in the septic shock group compared with the severe sepsis group (splanchnic DO2 175 +/- 19 ml/min per m2, splanchnic VO2 61 +/- 6 ml/min per m2). Gastric mucosal pH was subnormal in both groups (septic shock 7.29 +/- 0.02, severe sepsis 7.25 +/- 0.02) with no significant difference. No significant differences between groups were detected in lactate values. CONCLUSION: These data confirm a redistribution of blood flow to the splanchnic region in sepsis that is even more pronounced in patients with septic shock requiring norepinephrine. However, subnormal gastric mucosal pH suggested inadequate oxygenation in parts of the splanchnic region due to factors other than splanchnic hypoperfusion. Progress in this area will depend on techniques that address not only total splanchnic blood flow, but also inter-organ flow distribution, intra-organ distribution, and other microcirculatory or metabolic malfunctions.

Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract.

BACKGROUND: The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased. METHODS: 213 patients with carcinomas of the upper digestive tract were evaluated regarding their drinking habits. Chronic alcoholics met either the DSM-III-R criteria for alcohol abuse or dependence. Conventional laboratory markers and serum carbohydrate-deficient transferrin were determined preoperatively. Major intercurrent complications during ICU stay such as an alcohol withdrawal syndrome, pneumonia and sepsis as well as the frequency of death were documented. RESULTS: Patients did not differ significantly between groups regarding age or APACHE score on admission to the ICU.121 patients were diagnosed as being chronic alcoholics, 39 as being social drinkers and 61 as being non-alcoholics. In chronic alcoholics the frequency of death was significantly increased. Due to the increased incidence of pneumonia and sepsis the ICU stay was significantly prolonged in chronic alcoholics by approximately 8 days. CONCLUSIONS: The increased mortality and morbidity rate demonstrates that chronic alcoholics undergoing major tumor surgery have to be considered as high-risk patients during their postoperative ICU stay. Further studies are required with respect to the immuno-competence of chronic alcoholics and the prevention of alcohol withdrawal syndrome, pneumonia and sepsis in these patients.

Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma.

OBJECTIVE: A chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increased. DESIGN: Prospective study. SETTING: An intensive care unit. PATIENTS: A total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group. met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was > or = 60 g. Diagnostic indicators included an alcoholism-related questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin. MEASUREMENT AND RESULTS: Major intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (p = 0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days. CONCLUSIONS: Chronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop more major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

[The effect of prophylactically administered n-acetylcysteine on clinical indicators for tissue oxygenation during hyperoxic ventilation in cardiac risk patients]. / Einfluss der prophylaktischen Gabe von N-Azetylzystein auf klinische Indikatoren der Gewebeoxygenierung unter Hyperoxie bei kardialen Risikopatienten.

UNLABELLED: Hyperoxic ventilation, used to prevent hypoxia during potential periods of hypoventilation, has been reported to paradoxically decrease whole-body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve VO2 and other clinical indicators of tissue oxygenation in cardiac risk patients. METHODS: Thirty patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) because of cardiac risk factors, were included in this randomized investigation. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, F1O2 < 0.5). Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg kg-1 NAC (n = 15) or placebo (n = 15) in 250 ml 5% dextrose i.v. over a period of 30 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (F1O2 = 1.0), and 30 min after resetting the original F1O2. RESULTS: There were no significant differences between groups in any of the measurements before treatment and after the return to baseline F1O2 at the end of the study, respectively. NAC, but not placebo infusion, caused a slight but not significant increase in cardiac index (CI), left ventricular stroke work index (LVSWI) and a decrease in systemic vascular resistance. Significant differences between groups during hyperoxia were: VO2 (NAC: 108 +/- 38 ml min-1m-2 vs placebo: 79 +/- 22 ml min-1m-2; P < or = 0.05), CI (NAC: 4.6 +/- 1.0 vs placebo: 3.7 +/- 1.11 min-1m-2; P < or = 0.05) and LVSWI (NAC: 47 +/- 12 vs placebo: 38 +/- 9; P < or = 0.05). The mean decrease of VO2 was 22% in the NAC group vs 47% in the placebo group (P < or = 0.05) and the mean difference between groups in venoarterial carbon dioxide gradient (PvaCO2) was 14% (P < or = 0.05). ST segment depression ( > 0.2 mV) was significantly less marked in the NAC group (NAC: -0.02 +/- 0.17 vs placebo: -0.23 +/- 0.15; P < or = 0.05). CONCLUSIONS: NAC helped preserve VO2, oxygen delivery, CI, LVSWI and PvaCO2 during brief hyperoxia in cardiac risk patients. Clinical signs of myocardial ischemia did not occur such as ST-depression if patients were prophylactically treated with NAC. This suggests that pretreatment with NAC could be considered to attenuate impaired tissue oxygenation and to preserve myocardial performance better in cardiac risk patients during hyperoxia.

Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.

OBJECTIVES: To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. DESIGN: A prospective, randomized, blinded, controlled clinical trial. SETTING: A university hospital ICU. PATIENTS: Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. INTERVENTIONS: Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). MEASUREMENTS AND MAIN RESULTS: The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. CONCLUSIONS: There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.

Dopexamine hydrochloride in septic shock.

OBJECTIVE: To test whether dopexamine hydrochloride, by its beta 2-adrenoreceptor and dopaminergic 1 (DA1) and dopaminergic 2 (DA2) agonistic properties, can improve oxygen consumption (VO2) in hyperdynamic patients with septic shock. DESIGN: Prospective, single-cohort study. SETTING: ICU, university hospital. PATIENTS: Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. INTERVENTIONS: Short-term application (30 min) of dopexamine hydrochloride at a dose of 2 microgram/kg/min. MEASUREMENTS: Complete hemodynamic profile with O2 transport-related variables at baseline, 30 min after starting the dopexamine infusion, and 30 min after stopping the infusion. MAIN RESULTS: The dopexamine infusion resulted in significant increases in cardiac index (17%) (p<0.001) and O2 delivery (DO2) (16%) (p<0.001). VO2 increased slightly but significantly about 4% (p<0.001) by respiratory gas exchange measurements and 9% (p<0.001) by cardiovascular Fick calculations. The O2 extraction ratio decreased about 8% (0.001). CONCLUSIONS: The addition of dopexamine hydrochloride at a dose of 2 microgram/kg/min resulted in significant increases of DO2 and to a lesser extent VO2. Much of the global DO2 increase was not utilized, because O2 extraction ratio decreased. Direct calorigenic effects of dopexamine and an increase in myocardial VO2 likely account for a large portion of the increase in global VO2. Whether any of the VO2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.

Hypertonic saline in stabilized hyperdynamic sepsis.

Hypertonic saline with or without colloidal solution has been successfully used for treating hemorrhagic shock in animal experiments and clinical studies. Due to its various effects at systemic, organ, and microcirculatory levels, the substance appears to be a promising candidate for improving tissue oxygenation in sepsis. We therefore investigated the hypothesis that infusion of hypertonic saline would further improve O2 delivery, O2 extraction, and O2 uptake in hyperdynamic septic shock patients already stabilized by adequate volume and catecholamine infusion. Twenty-one patients received 2-4 mL/kg body weight of hypertonic saline in hydroxyethyl starch within 15 min. This hypertonic saline infusion caused a rapid significant increase in O2 delivery by 14% but only a marginal increase in O2 consumption (7% by cardiovascular Fick [p < .05], 4% by respiratory gases [n.s.]). Hypertonic saline increased the already elevated cardiac output by 24%. The pulmonary capillary wedge pressure increased from 14 +/- 3 to 23 +/ 3 mmHg and pulmonary shunt fraction increased 15%, but arterial PO2 did not fall. Except for the increase in pulmonary capillary wedge pressure, none of the cardiovascular changes lasted longer than 60 min. Plasma sodium levels increased from 138 +/- 25 to 163 +/- 38 mmol/L and normalized within 24 h. In these hyperdynamic septic patients, hypertonic saline infusion produced a transient increase in circulation, but no evidence of a substantial increase in O2 consumption. Either there was no significant O2 debt due to the already elevated O2 delivery levels at baseline (700 mL/min/m2) or the global O2 measurements we used were not able to detect discrete regional hypoxia.

Beta-carbolines in chronic alcoholics following trauma.

In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether beta-carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was > or =60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate-deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.

Prophylaxis of alcohol withdrawal syndrome in alcohol-dependent patients admitted to the intensive care unit after tumour resection.

Prophylaxis of alcohol withdrawal syndrome (AWS) in alcohol-dependent patients shortens the duration of stay in the intensive care unit (ICU). The objective of this study was to assess the effect of four different prophylactic regimens on the duration of ICU stay, prevention of AWS and rate of major intercurrent complications in alcohol-dependent patients admitted to the ICU after tumour resection. A total of 197 alcohol-dependent patients, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (third revised edition) with a daily ethanol intake of 60 g, were allocated randomly to one of the following regimens which were commenced on admission to the ICU: flunitrazepam-clonidine, chlormethiazole-haloperidol, flunitrazepam-haloperidol or ethanol. The duration of ICU stay, prevention of AWS, incidence of tracheobronchitis and major intercurrent complications such as pneumonia, sepsis, cardiac disorders, bleeding disorders and death were documented. On admission, patients did not differ significantly in age, APACHE II and multiple organ failure scores. ICU stay, incidence of AWS, severity of AWS (revised clinical institute withdrawal assessment for alcohol scale > 20) and major intercurrent complication rate did not differ significantly between groups. Although there was no advantage in any of the four regimens with respect to the primary outcome measures, pulmonary and cardiac patients were not included in the study. Patients in the chlormethiazole-haloperidol group had a significantly increased incidence of tracheobronchitis (P = 0.0023), probably because of an increased incidence of hypersecretion.

Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock.

OBJECTIVES: To test whether dopamine infusion improves oxygen delivery (Do2) and oxygen uptake (VO2) in hyperdynamic septic shock patients stabilized by adequate volume and dobutamine alone, or by the combination of dobutamine and norepinephrine. DESIGN: Prospective clinical trial of two patient groups. Group 1 (n = 15) was stabilized with dobutamine, and group 2 (n = 10) was stabilized with dobutamine and norepinephrine. SETTING: Intensive care unit in a university hospital. PATIENTS: Twenty-five postoperative, hyperdynamic septic shock patients. INTERVENTIONS: The stabilizing catecholamine infusion was replaced in a stepwise manner by dopamine to achieve a similar mean arterial pressure (dopamine doses: group 1, mean 22 +/- 15 micrograms/kg/min [range 6 to 52]; and group 2, mean 57 +/- 41 micrograms/kg/min [range 15 to 130]). MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was performed with oxygen transport-related variables at baseline, after replacement by dopamine, and after resetting to the original catecholamine infusion. The change to dopamine resulted in increases in cardiac index (group 1: 20% [p < .01]; group 2: 33% [p < .01]), and DO2 (group 1: 19% [p < .01]; group 2: 27% [p < .01]). However, VO2, whether directly measured from the respiratory gases or calculated by the cardiovascular Fick principle, did not change in both groups with dopamine, while the oxygen extraction ratio decreased significantly in both groups with dopamine. Heart rate, pulmonary artery occlusion pressure, and pulmonary shunt fraction all increased with dopamine. PaO2 decreased, but oxygen saturation remained stable in both groups with dopamine. CONCLUSIONS: Short-term dopamine infusion in hyperdynamic septic shock patients, despite producing higher global DO2, was not superior to dobutamine or the combination of dobutamine and norepinephrine infusion.

Relevance of carbohydrate-deficient transferrin as a predictor of alcoholism in intensive care patients following trauma.

Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patient's history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-carbolines in chronic alcoholics undergoing elective tumor resection.

The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether beta-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was > or = 60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norharman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.

[Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Therapeutic value of treatment with calcium antagonists, hypervolemic hemodilution and induced arterial hypertension]. / Zerebraler Vasospasmus nach aneurysmatischer Subarachnoidalblutung. Therapeutischer stellenwert von Kalziumantagonisten, hypervolämischer Hämodilution und induzierter arterieller Hypertension.

Only 53%-58% of patients with a subarachnoid haemorrhage (SAB) following the rupture of a cerebral aneurysm survive without neurological damage. Morbidity and mortality are closely related to the delayed ischaemic neurological deficit due to cerebral vasospasm. The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature. PATHOPHYSIOLOGY. In addition to other vasoactive substances in the blood, haemoglobin, which is released from lysed erythrocytes on the 2nd to 4th day after the haemorrhage, plays an important role in inducing vasospasm. An inflammatory angiopathy ensues, with complete resolution after 6-12 weeks. The cerebral blood flow (CBF) is reduced depending on the extent of vasospasm. Irreversible infarction may follow the decrease of CBF below a critical value. Severe vasospasm causes autoregulatory disturbances and reduced responsiveness of cerebral vessels to CO2. CALCIUM ANTAGONISTS. The calcium blocker nimodipine causes dilatation of small pial vessels with increased CBF. However, systemic vasodilation with the subsequent fall in blood pressure may limit the increase in CBF. Furthermore, it is known that nimodipine decreases intracellular calcium concentrations resulting in some protection against ischaemic cellular injury. Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm. HYPERVOLAEMIC HAEMODILUTION. Volume expansion and haemodilution to a hematocrit of 30%-33% is suggested to improve cerebral perfusion during vasospasm. The central venous and pulmonary capillary wedge pressures should be 10-12 mm Hg and 15-18 mm Hg, respectively. But there is no evidence of improved outcome with this measure, and pulmonary edema is a frequent side effect. However, impairment of cerebral perfusion and increased neurological damage can be demonstrated with hypovolaemia and haemoconcentration. INDUCED ARTERIAL HYPERTENSION. In the presence of cerebral vasospasm and resulting autoregulatory disturbances, cerebral perfusion can be increased by raising systemic arterial pressure. This measure, too, fails to improve neurological outcome. CONCLUSION. Treatment of cerebral vasospasm following a SAB aims to avoid any impairment of cerebral perfusion. Hypovolaemia and haemoconcentration have to be corrected. Normoventilation should be established to avoid hypocapnic vasoconstriction. Nimodipine should be administered continuously after a SAB. In view of the autoregulatory disturbances, systemic hypotension with its danger of decreased CBF must be prevented. The importance of hypervolaemic haemodilution and/or induced arterial hypertension is not clear. Despite therapeutic efforts, the number of patients who have survived a SAB without a substantial neurological deficit has not increased.

Excessive hypokalemia and hyperkalemia following head injury.

A sudden decrease of serum potassium below 2.5 mmol/l carries the risk of dangerous arrhythmias and requires immediate replacement therapy [6]. We refer to a patient with a brain stem compression after head injury, who developed a profound hypokalemia (K+ = 1.2 mmol/l) with life-threatening arrhythmias, probably due to a catecholamine induced intracellular potassium shift (beta-2-stimulation). Only by aggressive potassium replacement up to 80 mmol/h (610 mmol/16 h) could potassium levels be increased and cardiac arrhythmias terminated. Although replacement therapy was stopped when the serum K(+)-level increased to 2.4 mmol/l, 3.5 h later the patient became hyperkalemic (8.1 mmol/l). This was probably due to a secondary shift of potassium from intra- to extracellular space. In patients with severe head trauma and the potential risk of excessive catecholamine release special attention must be paid to changes in potassium balance.