L. Hannemann

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.

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.

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 unitPatients: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 μg/kg per min). Low-dose dopamine had 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.

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

ObjectiveA 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 increasedDesignProspective study.SettingAn intensive care unit.PatientsA 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 ≥60 g. Diagnostic indicators included an alcoholismrelated questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin.Measurement and resultsMajor 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.ConclusionsChronic 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 mor 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.

Optimal oxygen delivery in critically ill patients

Standard hemodynamic support in septic shock is to increase pulmonary capillary wedge pressure to above 15 mmHg by volume replacement and to give inotropic support if the mean arterial pressure (MAP) is not adequate. In an attempt to decrease mortality in critically ill patients, oxygen delivery (DO2) was increased by switching inotropic support from dobutamine alone or in combination with norepinephrine to dopamine alone, or by adding dopexamine, prostacyclin, or hypertonic saline to the treatment. DO2 increased significantly in all patients, but the increase in DO2 was accompanied by only a 10% increase in oxygen consumption (VO2). The increase in VO2 was similar in survivors and nonsurvivors and in patients with and without septic shock. The results indicate that if adequate volume and inotropic support is provided for critically ill patients, the detectable oxygen debt is small and has little effect on patient outcome. When DO2 is adequate, factors other than a tissue oxygen deficit seem to determine patient outcome.

The Relationship Between Mixed Venous and Hepatic Venous O2 Saturation in Patients With Septic Shock

It was the purpose of this study to measure the relationship between hepatic venous O2 saturation (ShvO2) and mixed venous O2 saturation (SvO2) in septic patients (n = 21) following treatment with various catecholamines (epinephrine, norepinephrine, dopamine, dopexamine). At baseline mean SvO2 was 74 +/- 5% while mean ShvO2 was 59 +/- 12%. Alpha-mimetic substances such as epinephrine and norepinephrine reduced ShvO2 and increased the difference between SvO2 and ShvO2.Beta2-mimetic and dopaminergic substances (dopexamine, dopamine) did not change the difference between SvO2 and ShvO2. These results show that SvO2 does not necessarily reflect all changes of ShvO2. Monitoring ShvO2 may be helpful in managing septic shock by adding information on adequacy of O2 supply/consumption ratio in the crucial splanchnic region.

β‐Carbolines in chronic alcoholics following trauma

In our society every second polytraumatized patient is a chronic alcoholic. A patients 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 β‐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 ≥ 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.

[The effect of prophylactically administered n-acetylcysteine on clinical indicators for tissue oxygenation during hyperoxic ventilation in cardiac risk patients].

ZusammenfassungHyperoxische Ventilation wird oft prophylaktisch angewandt. Dabei kommt es zu einem Abfall des globalen Sauerstoffverbrauchs (VO2), bei kardialen Risikopatienten zu einer Exazerbation von myokardialen Ischämien. N-Azetylzystein (NAC) kann den VO2 und die myokardiale Kontraktilität verbessern. Wir untersuchten, ob NAC unter Hyperoxie einen Einfluß auf klinische Parameter der Gewebeoxygenierung bei kardialen Risikopatienten hat. 30 Patienten, bei denen aufgrund ihrer kardialen Grunderkrankung ein erweitertes hämodynamisches Monitoring durchgeführt wurde, erhielten nach einer Ausgangsmessung randomisiert entweder 150 mg kg−1NAC (n=15) oder Plazebo (n=15) i.v. über einen Zeitraum von 30 min. Die Messungen fanden 30 min nach NAC- oder Plazebogabe, 30 min nach hyperoxischer Ventilation und 30 min nach Ventilation unter der Ausgangs-FIO2statt. Signifikante Unterschiede fanden sich unter Hyperoxie zwischen den beiden Gruppen im Hinblick auf den VO2, den Herzindex und die linksventrikuläre Schlagarbeit. Der mittlere Abfall des VO2betrug in der NAC-Gruppe 22% und in der Plazebogruppe 47% (p≤0,05). Der venoarterielle CO2-Gradient lag in der NAC-Gruppe um 14% höher (p≤0,05). Die ST-Strecken-Senkung war unter NAC geringer (p≤0,05). Diese Ergebnisse könnten darauf hinweisen, daß die prophylaktische Gabe von NAC bei kardialen Risikopatienten zu einer verbesserten Gewebeoxygenierung unter Hyperoxie beitragen kann.AbstractHyperoxic 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, FIO2<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 (FIO2=1.0), and 30 min after resetting the original FIO2. Results. There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 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≤0.05), CI (NAC: 4.6±1.0 vs placebo: 3.7±1.11 min−1m−2; P≤0.05) and LVSWI (NAC: 47±12 vs placebo: 38±9; P≤0.05). The mean decrease of VO2 was 22% in the NAC group vs 47% in the placebo group (P≤0.05) and the mean difference between groups in venoarterial carbon dioxide gradient (PvaCO2) was 14% (P≤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≤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.

Oxygen Transport Related Variables and Muscle Tissue Oxygenation in Critically Ill Patients with and Without Sepsis

Impaired tissue oxygenation and tissue hypoxia are considered to be the final common pathway of the various clinical insults that are responsible for the development of multiple systems organ failure (Sibbald et al., 1989). It was hypothesized that, in sepsis and ARDS patients tissue hypoxia may exist despite normal or even supranormal convective O2-transport to tissues by reduced O2 extraction capacity (Schumaker, Cain, 1987). In various clinical studies supply dependency of O2 uptake (VO2) has been demonstrated in patients with sepsis and ARDS (Danek et al., 1980, Mohsenifar et al., 1983, Bihari et al. 1987) which was interpreted as the indirect proof for the existance of a covert tissue hypoxia (Bihari et al., 1987). To test this hypothesis we compared variables related to hemodynamics- and oxygen transport — in two groups of critically ill patients.

The Relevance of Measuring O2 Supply and O2 Consumption for Assessment of Regional Tissue Oxygenation

Septic shock and ARDS are associated with disturbed tissue oxygenation. It has been suggested to increase O2 supply (DO2) above the normal level (> 600 ml/min/m2) to compensate for the tissue hypoxia. The lack of a rise in O2 consumption (VO2) after increases of DO2 has been presumed to indicate adequate tissue oxygenation (negative O2 flux test). We were interested in whether a negative O2 flux test precludes an improvement of regional tissue oxygenation. The pH value of the gastric mucosa (pHi) is considered to be a sensitive marker for hypoxia in the splanchnic region. We measured pHi as well as DO2 and VO2 in 10 patients with hyperdynamic septic shock to assess the effect of volume substitution on tissue oxygenation. The initial therapeutic approach (volume substitution and catecholamines) led to a DO2 of 717 +/- 187 ml/min/m2. However, all patients had pHi values < 7.35 indicating regional tissue hypoxia. An additional increase of DO2 by colloidal volume substitution caused a significant rise of pHi from 7.20 +/- 0.05 to 7.25 +/- 0.05 but did not change VO2. We conclude that a negative O2 flux test does not rule out regional tissue hypoxia, and second, an increase in DO2 may improve tissue oxygenation without measurable changes in VO2. Furthermore, adequate volume substitution is an important step in the treatment of septic shock to increase total body blood flow and more specifically regional blood flow.