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Prognostic value of blood lactate in critically ill patients
141
ll(1984) 141-146 Scientific Publishers Ireland Ltd.
Resuscitation, Elsevier
Review Paper
PROGNOSTIC VALUE ILL PATIENTS
HANSPETER II. Medizinische Maim F.R.G.
OF BLOOD LACTATE
IN CRITICALLY
SCHUSTER
Klinik, Johannes Gutenberg-Universitlt
Mains, Langenbeckstrasse
1, D-6500
(Received July 25th, 1983)
SUMMARY Hyperlactatemia is frequently observed in critically ill patients. A correlation of blood lactate concentrations and outcome of patients has been proven in circulatory shock, circulatory arrest, acute myocardial infarction, acute hypnotic drug poisoning and severe pancreatitis. However, the prognostic relevance of hyperlactatemia yields from statistical examinations in larger groups of patients. It should not be misused as a reliable prognostic sign in the individual patient, but is of high value in comparing groups of patients. In individual patients, hyperlactatemia is a useful indicator pointing to the severity of illness and to superimposed complications. Blood lactate is of considerable value for the metabolic monitoring of critically ill patients.
Hyperlactatemia is often seen in critically ill patients (v. Wichert and Bergengruen, 1971; Kiinigshausen, Hein, Schnurr and Grabensee, 1978). Hyperlactatemia appears, when lactate production is increased and removal of lactate is deficient (Cohen and Simpson, 1975). Basic etiologic conditions of hyperlactatemia are disorders of cell metabolism and cell hypoxia arising from decreased oxygen supply to tissues (Table I). Hyperlactatemia due to distortion of cell metabolism has been ascribed to the action of toxic substances and drugs and to liver failure. Hyperlactatemia of cell hypoxia may result from hypoperfusion of tissues due to low cardiac output and arterial hypotension, from obstruction of microvasculature in Resent
address: Stiidtisches Krankenhaus,
Hochschule
Hannover,
Weinberg
Akademisches Lehrkrankenhaus 1, D-3200, Hildesheim, F.R.G.
0300-9572/84/$03.00 @ 1984 Elsevier Scientific Printed and Published in Ireland
Publishers
Ireland Ltd.
der Medizinischen
142 TABLE I HYPERLACTATEMIA IN CRITICALLY ILL PATIENTS ETIOLOGY LXsora!er8of cell metabolism (A) Toxic substances and drugs Cyanide Phenformin Salicylates Epinephrine Ether Methanol Ethanol (B) Liver failure Cell hypoxia (A) Left ventricular failure Low cardiac output Hypotension Pulmonary edema (B) Disseminated intravascular coagulation (C) Severe hypoxemia Respiratory failure Pulmonary edema
disseminated intravascular coagulation, and from severe hypoxemia in respiratory failure and pulmonary edema. Cell hypoxia is apparently the chief cause of hyperlactatemia in intensive care patients. HYPERLACTATEMIA IN CIRCULATORY SHOCK
Peretz, McGregor and Dossetor (1964) and Broder and Weil (1964) were the first to report that hyperlactatemia was of considerable prognostic value in predicting the outcome of shock. A high lactate concentration determined early in shock can be associated with a high mortality rate. Peretz, Scott, Duff, Dossetor, MacLean and McGregor (1965) published a graph assigning the relationship between blood lactate levels determined early in shock, and mortality rate. With increasing lactate concentrations, mortality rate increased and only 1 out of 18 patients survived in whom lactate exceeded 8.9 mmol/l. Weil and AHi (1970) published a well known diagram which covered their results of extensive investigations on the behaviour of lactate and pyruvate in experimental as well as in clinical shock. They found a significant correlation between blood lactate concentrations and the outcome of shock, and this relationship could be defined mathematically. As lactate increased from 2 to 8 mmol/l, the estimated probability of survival decreased from 90% to 10%. The probability of misclassification was said to be only 12%. The
143
knowledge of the lactate/pyruvate ratio offered no advantage over that of blood lactate in predicting the outcome of shock. However, the quantification of the correlation between lactate concentrations and survival depends not only upon the severity but also upon the etiology of shock. Vitek and Cowley (1971) compared blood lactate and survival in different forms of shock. The curve of probability of survival derived from pooled lactate data of all shock patients was very simular to that of Weil and Afifi. A comparison of the curves of survival probability for various groups of shock, however, demonstrated considerable differences. The authors defined the lactate levels for 50% survival probability as SLW. The SLm point was 7.3 mmol/l for hemorrhagic-traumatic shock and only 3.5 mmol/l for septic shock. Perret, Enrico and Poli (1970/71) and Perret, Poli and Enrico (1969/70) pointed out that the relationship between maximal blood lactate concentration and mortality rate is essentially influenced by liver function. ‘In pure septic shock with increased liver perfusion, low lactate levels (below 3.5 mmol/l) may go on with a high mortality rate, and in patients with cirrhosis of the liver and reduced metabolism of lactate by the liver high lactate levels (above 11 mmol/l) may be observed in patients who survive. BLOOD LACTATE
IN CIRCULATORY
ARREST
Rackwitz, Jahrmlrker, The&n, Halbritter, Otter and Haider (1975) studied blood lactate in circulatory arrest due to cardiac standstill or ventricular fibrillation. There was an even higher increase in blood lactate concentration as compared to circulatory shock. In 38 patients under the condition of cardiopulmonary resuscitation lactate was analysed in lo-ZO-min intervals up to 60-80 min from the beginning of cardiopulmonary resuscitation. In 11 patients who died after unsuccessful CPR, there was a steep increase in blood lactate. The calculated mean increase in lactate was approximately 3 mmol/l/lO min of cardiac massage. This was significantly higher than the calculated increase of blood lactate in shock, which was approximately 0.8 mmol/l per 10 min. In seven patients who survived after successful CPR, a rapid decrease in blood lactate was observed. The decrease in lactate concentration was between 4 and 10 mmol/l per 10 min. In uncomplicated cases blood lactate was usually normalised after 4 h. Persistent high levels (>6mmol/l) or even increasing concentrations indicated circulatory insufficiency or hepatic failure and bore a poor prognosis. BLOOD LACTATE
IN ACUTE MYOCARDIAL
INFARCTION
Gallitz, Sandel, Jahrmtirker, Rackwitz and Haider (1975) investigated the significance of blood lactate in acute myocardial infarction. In 89 patients .
144
they demonstrated a significant correlation between survival and blood lactate concentrations upon admission to the coronary care unit (up to 24 h after the onset of symptoms). In patients with blood lactate above 3 mmol/l mortality was about 70%. The differences in mortality between patients with blood lactate above 3mmol/l and those with blood lactate concentrations below 3 mmol/l was highly significant (p < 0.001). In a more recent publication Jahrmlirker, Halbritter, Haider and Rackwitz (1981) investigated the prognostic value of repeated estimations of blood lactate during acute myocardial infarction. For any given point in time during the course of infarction, repeated lactate levels within the normal range (<1.5 mmol/l) indicated a lethality between 0% and 22% for the individual patient. Lactate values between 1.5 and 4 mmol/l increased the probability of non-survival to 2244%. Persistent levels above 4mmol/l had a mortality rate between 58% and 100%. BLOOD LACTATE
IN HYPNOTIC DRUG POISONING
Schuster, Kapp, Prellwitz, Gunther and Weilemann (1980) and Schuster, Kapp, Prellwitz, Schuster and Weilemann (1981) studied blood lactate in patients with acute hypnotic drug poisoning. Thirty-five unconscious patients with hypnotic drug poisoning were investigated. Rlood lactate was detern+ated enzymatically on admission as soon as respiration was under control and arterial blood gases and pH kept within normal limits. Repeated blood samples were drawn from central venous catheters in 6-12-h intervals. Only two of the severely poisoned patients had clinical manifestations of circulatory shock. Body temperature was below 35°C in 6 patients. Poisoning was due to 16 different types of drugs. Lactate concentration was above 2mmoUl in 15 out of 17 patients with moderate poisoning and in 17 out of 18 patients with severe poisoning. On admission, blood lactate was significantly higher in severe intoxicated patients (3.90 + 2.94 mmol/l) in comparison to a control group of unpoisoned patients (1.25+ 0.17 mmol/ll. Blood lactate was less elevated in moderate poisoning (2.7 + 1.22 mmol/l) with a considerable overlapping of values between the two groups of severe and moderate poisoning. Thirty-six hours after admission blood lactate was completely normalized in patients with moderate intoxication (1.19 +-0.96 mmol/l), but was still significantly elevated in severely poisoned subjects (2.26 f 1.48 mmol/ll. A statistically significant linear correlation could be determined between the duration of unconsciousness and the maximal concentrations found within 12 h upon admission on the basis of lactate estimations in 6-h intervals. This was true in patients with moderate poisoning as well as in patients with severe poisoning. Hyperlactatemia in acute hypnotic drug poisoning is most likely due to hypoperfusion of tissues, arising from cardio-circulatory derangements like
145
low cardiac output, compromised myocardial performance, disturbed peripheral perfusion and disseminated intravascular clothing (Wright, Clarkson, Brown and Faster, 1971). The fact that no distinction could be made between different types of ingested drugs argues against direct toxic action upon cell metabolism as the cause of hyperlactatemia in hypnotic drug poisoning. However, in patients who ingested alcohol in addition to hypnotic drugs toxic ethanol effects may have contributed to the elevation of blood lactate (Levy, Elo and Handenson, 1977). BLOOD LACTATE
IN ACUTE
PANCREATITIS
In patients with acute pancreatitis, preliminary data of Schiinborn and Kiimmerle (1978) point to an interrelationship between blood lactate and severity of illness. A worse clinical course was accompanied by high lactate levels. Post surgery, surviving patients developed normal lactate levels, whereas hyperlactatemia persisted in non-suvivors. CONCLUSIONS
Hyperlactatemia is a useful indicator of the severity of illness and is helpful in detecting superimposed complications in the critically ill. Mathematically defined correlations between lactate levels and survival should not be overstressed and often fail in the individual patient. Repeated determinations are more useful than a single value. Persistently high or progressively rising concentrations point to the need for improvement of the therapeutic regimen in the individual patient. Persistently high or progressively rising concentrations, inspite of adequate therapy, indicate a poor prognosis. For the individual patient, blood lactate estimation is less variable as a prognostic index discriminating between survival and nonsurvival, but it is of considerable value as a method for metabolic monitoring. REFERENCES Broder, G. and WeiI. M.H. (1964) Excess lactate: An index of reversibility of shock in human patients. Science, 143, 1457-1459. Cohen, R.D. and Simpson, R. (1975) Lactate metabolism. Anesthesiology, 43,661-673. Gallitz, T. Sandel, P., Jahmiirker, H., Rackwitz, R. and Haider, M. (19751 Ein prognostischer Index bei akutem Myokardinfarkt. Dtsch. Med. Wochenschr., 100,2517-2523. Jahrmlrker, H., Halbritter, R., Haider, M and Rackwitx, R. (1981) Prognostik und prognostische Parameter als Grundlage therapeutischer Entscheidungen in der Intensivmedixin. Internist, 22, 131-149. Kiinigshausen, Th., Hein, D., Schnurr, E. and Grabensee, B. (1978) Liquor-Lactat und Elektroenxephalogramm bei komat&en Patienten im Rahmen interner Krankheitsbilder. Dtsch. Med. Wochenschr., 103,99%1006. Levy, R., Elo, T. and Hanenson, I.B. (1977) Intravenous fructose treatment of acute alcohol intoxication. Arch. Intern. Med., 137, 117-&1177. Peretz, D.I., McGregor M. and Doesetor, J.B. (1964) Lactic acidosis: A clinically significant aspect of shock. Can. Med. Assoc. J.. 90,673+75.
146 Peretz, D.I., Scott, H.M., Duff, J., Dossetor, J.B., MacLean, L.D. and MacGregor, M. (19651 The significance of lacticacidemia in the shock syndrome. Ann. N.Y. Acad. Sci. 119, 1133-1141. Perret, C., Enrico, J.F. And Poli, S. (1970/71) Acid-base disturbances and lactate metabolism in shock (Abstract). Eur. J. Clin. Invest. 1, 387. Perret, C., Poli, S. and Enrico, J.F. (1969/701 Lactic acidosis and liver damage. Helv. Med. Ada, 35,377405. Rackwits, R., Jahrmiirker, H., Theisen, K., Halbritter, R., Otter, H.P. and Haider, M. (1975) Pathogenese und Therapie der Axidose bei Reanimation. Intensivmedizin, 12, l-23. Schiinbom, H., Kiimmerle, F. (1978) Die akute Pankreatitis und ihre Intensivtherapie. Intensivmedixin, 15, 39-44. Schuster, H.P., Kapp, S., Prellwitz, W., Schuster, C.J. and Weilemann L.S. (1981) Significance of hyperlactatemia in acute hypnotic drug poisoning. Klin. Woschenschr., 59, 599-605. Schuster, H.P., Prellwitz, W., Gunther, R., Kapp, S. and Weilemann, L.S. (1981) Verlaufsanalyse der Hyperlaktatiimie bei Patienten mit akuten Schlafmittelvergiftungen unterschiedlicher Schweregrade. Intensivmedizin, 18, 150-155. Vitek, V. and Cowley, R.A. (1971) Blood lactate in the prognosis of various forms of shock. Ann. Surg., 173, 308-313. Weil, M.H. and Afifi, A.A. (1970) Experimental and clinical studies of lactate and pyruvate as indicators of the severity of acute circulatory failure (Shock). Circulation, 41, 989-1001. von Wichert, P. and Bergengruen, 0. (1971) Laktat-Bestimmung im Blut. Med. Welt., 18, 752-756. Wright, N., Clarkson, A.R., Brown, S.S. and Fuster, V. (19711 Effects of poisoning on serum enzyme activities, Coagulation, and fibrinolysis. Br. Med. J., 3, 347350.
ll(1984) 141-146 Scientific Publishers Ireland Ltd.
Resuscitation, Elsevier
Review Paper
PROGNOSTIC VALUE ILL PATIENTS
HANSPETER II. Medizinische Maim F.R.G.
OF BLOOD LACTATE
IN CRITICALLY
SCHUSTER
Klinik, Johannes Gutenberg-Universitlt
Mains, Langenbeckstrasse
1, D-6500
(Received July 25th, 1983)
SUMMARY Hyperlactatemia is frequently observed in critically ill patients. A correlation of blood lactate concentrations and outcome of patients has been proven in circulatory shock, circulatory arrest, acute myocardial infarction, acute hypnotic drug poisoning and severe pancreatitis. However, the prognostic relevance of hyperlactatemia yields from statistical examinations in larger groups of patients. It should not be misused as a reliable prognostic sign in the individual patient, but is of high value in comparing groups of patients. In individual patients, hyperlactatemia is a useful indicator pointing to the severity of illness and to superimposed complications. Blood lactate is of considerable value for the metabolic monitoring of critically ill patients.
Hyperlactatemia is often seen in critically ill patients (v. Wichert and Bergengruen, 1971; Kiinigshausen, Hein, Schnurr and Grabensee, 1978). Hyperlactatemia appears, when lactate production is increased and removal of lactate is deficient (Cohen and Simpson, 1975). Basic etiologic conditions of hyperlactatemia are disorders of cell metabolism and cell hypoxia arising from decreased oxygen supply to tissues (Table I). Hyperlactatemia due to distortion of cell metabolism has been ascribed to the action of toxic substances and drugs and to liver failure. Hyperlactatemia of cell hypoxia may result from hypoperfusion of tissues due to low cardiac output and arterial hypotension, from obstruction of microvasculature in Resent
address: Stiidtisches Krankenhaus,
Hochschule
Hannover,
Weinberg
Akademisches Lehrkrankenhaus 1, D-3200, Hildesheim, F.R.G.
0300-9572/84/$03.00 @ 1984 Elsevier Scientific Printed and Published in Ireland
Publishers
Ireland Ltd.
der Medizinischen
142 TABLE I HYPERLACTATEMIA IN CRITICALLY ILL PATIENTS ETIOLOGY LXsora!er8of cell metabolism (A) Toxic substances and drugs Cyanide Phenformin Salicylates Epinephrine Ether Methanol Ethanol (B) Liver failure Cell hypoxia (A) Left ventricular failure Low cardiac output Hypotension Pulmonary edema (B) Disseminated intravascular coagulation (C) Severe hypoxemia Respiratory failure Pulmonary edema
disseminated intravascular coagulation, and from severe hypoxemia in respiratory failure and pulmonary edema. Cell hypoxia is apparently the chief cause of hyperlactatemia in intensive care patients. HYPERLACTATEMIA IN CIRCULATORY SHOCK
Peretz, McGregor and Dossetor (1964) and Broder and Weil (1964) were the first to report that hyperlactatemia was of considerable prognostic value in predicting the outcome of shock. A high lactate concentration determined early in shock can be associated with a high mortality rate. Peretz, Scott, Duff, Dossetor, MacLean and McGregor (1965) published a graph assigning the relationship between blood lactate levels determined early in shock, and mortality rate. With increasing lactate concentrations, mortality rate increased and only 1 out of 18 patients survived in whom lactate exceeded 8.9 mmol/l. Weil and AHi (1970) published a well known diagram which covered their results of extensive investigations on the behaviour of lactate and pyruvate in experimental as well as in clinical shock. They found a significant correlation between blood lactate concentrations and the outcome of shock, and this relationship could be defined mathematically. As lactate increased from 2 to 8 mmol/l, the estimated probability of survival decreased from 90% to 10%. The probability of misclassification was said to be only 12%. The
143
knowledge of the lactate/pyruvate ratio offered no advantage over that of blood lactate in predicting the outcome of shock. However, the quantification of the correlation between lactate concentrations and survival depends not only upon the severity but also upon the etiology of shock. Vitek and Cowley (1971) compared blood lactate and survival in different forms of shock. The curve of probability of survival derived from pooled lactate data of all shock patients was very simular to that of Weil and Afifi. A comparison of the curves of survival probability for various groups of shock, however, demonstrated considerable differences. The authors defined the lactate levels for 50% survival probability as SLW. The SLm point was 7.3 mmol/l for hemorrhagic-traumatic shock and only 3.5 mmol/l for septic shock. Perret, Enrico and Poli (1970/71) and Perret, Poli and Enrico (1969/70) pointed out that the relationship between maximal blood lactate concentration and mortality rate is essentially influenced by liver function. ‘In pure septic shock with increased liver perfusion, low lactate levels (below 3.5 mmol/l) may go on with a high mortality rate, and in patients with cirrhosis of the liver and reduced metabolism of lactate by the liver high lactate levels (above 11 mmol/l) may be observed in patients who survive. BLOOD LACTATE
IN CIRCULATORY
ARREST
Rackwitz, Jahrmlrker, The&n, Halbritter, Otter and Haider (1975) studied blood lactate in circulatory arrest due to cardiac standstill or ventricular fibrillation. There was an even higher increase in blood lactate concentration as compared to circulatory shock. In 38 patients under the condition of cardiopulmonary resuscitation lactate was analysed in lo-ZO-min intervals up to 60-80 min from the beginning of cardiopulmonary resuscitation. In 11 patients who died after unsuccessful CPR, there was a steep increase in blood lactate. The calculated mean increase in lactate was approximately 3 mmol/l/lO min of cardiac massage. This was significantly higher than the calculated increase of blood lactate in shock, which was approximately 0.8 mmol/l per 10 min. In seven patients who survived after successful CPR, a rapid decrease in blood lactate was observed. The decrease in lactate concentration was between 4 and 10 mmol/l per 10 min. In uncomplicated cases blood lactate was usually normalised after 4 h. Persistent high levels (>6mmol/l) or even increasing concentrations indicated circulatory insufficiency or hepatic failure and bore a poor prognosis. BLOOD LACTATE
IN ACUTE MYOCARDIAL
INFARCTION
Gallitz, Sandel, Jahrmtirker, Rackwitz and Haider (1975) investigated the significance of blood lactate in acute myocardial infarction. In 89 patients .
144
they demonstrated a significant correlation between survival and blood lactate concentrations upon admission to the coronary care unit (up to 24 h after the onset of symptoms). In patients with blood lactate above 3 mmol/l mortality was about 70%. The differences in mortality between patients with blood lactate above 3mmol/l and those with blood lactate concentrations below 3 mmol/l was highly significant (p < 0.001). In a more recent publication Jahrmlirker, Halbritter, Haider and Rackwitz (1981) investigated the prognostic value of repeated estimations of blood lactate during acute myocardial infarction. For any given point in time during the course of infarction, repeated lactate levels within the normal range (<1.5 mmol/l) indicated a lethality between 0% and 22% for the individual patient. Lactate values between 1.5 and 4 mmol/l increased the probability of non-survival to 2244%. Persistent levels above 4mmol/l had a mortality rate between 58% and 100%. BLOOD LACTATE
IN HYPNOTIC DRUG POISONING
Schuster, Kapp, Prellwitz, Gunther and Weilemann (1980) and Schuster, Kapp, Prellwitz, Schuster and Weilemann (1981) studied blood lactate in patients with acute hypnotic drug poisoning. Thirty-five unconscious patients with hypnotic drug poisoning were investigated. Rlood lactate was detern+ated enzymatically on admission as soon as respiration was under control and arterial blood gases and pH kept within normal limits. Repeated blood samples were drawn from central venous catheters in 6-12-h intervals. Only two of the severely poisoned patients had clinical manifestations of circulatory shock. Body temperature was below 35°C in 6 patients. Poisoning was due to 16 different types of drugs. Lactate concentration was above 2mmoUl in 15 out of 17 patients with moderate poisoning and in 17 out of 18 patients with severe poisoning. On admission, blood lactate was significantly higher in severe intoxicated patients (3.90 + 2.94 mmol/l) in comparison to a control group of unpoisoned patients (1.25+ 0.17 mmol/ll. Blood lactate was less elevated in moderate poisoning (2.7 + 1.22 mmol/l) with a considerable overlapping of values between the two groups of severe and moderate poisoning. Thirty-six hours after admission blood lactate was completely normalized in patients with moderate intoxication (1.19 +-0.96 mmol/l), but was still significantly elevated in severely poisoned subjects (2.26 f 1.48 mmol/ll. A statistically significant linear correlation could be determined between the duration of unconsciousness and the maximal concentrations found within 12 h upon admission on the basis of lactate estimations in 6-h intervals. This was true in patients with moderate poisoning as well as in patients with severe poisoning. Hyperlactatemia in acute hypnotic drug poisoning is most likely due to hypoperfusion of tissues, arising from cardio-circulatory derangements like
145
low cardiac output, compromised myocardial performance, disturbed peripheral perfusion and disseminated intravascular clothing (Wright, Clarkson, Brown and Faster, 1971). The fact that no distinction could be made between different types of ingested drugs argues against direct toxic action upon cell metabolism as the cause of hyperlactatemia in hypnotic drug poisoning. However, in patients who ingested alcohol in addition to hypnotic drugs toxic ethanol effects may have contributed to the elevation of blood lactate (Levy, Elo and Handenson, 1977). BLOOD LACTATE
IN ACUTE
PANCREATITIS
In patients with acute pancreatitis, preliminary data of Schiinborn and Kiimmerle (1978) point to an interrelationship between blood lactate and severity of illness. A worse clinical course was accompanied by high lactate levels. Post surgery, surviving patients developed normal lactate levels, whereas hyperlactatemia persisted in non-suvivors. CONCLUSIONS
Hyperlactatemia is a useful indicator of the severity of illness and is helpful in detecting superimposed complications in the critically ill. Mathematically defined correlations between lactate levels and survival should not be overstressed and often fail in the individual patient. Repeated determinations are more useful than a single value. Persistently high or progressively rising concentrations point to the need for improvement of the therapeutic regimen in the individual patient. Persistently high or progressively rising concentrations, inspite of adequate therapy, indicate a poor prognosis. For the individual patient, blood lactate estimation is less variable as a prognostic index discriminating between survival and nonsurvival, but it is of considerable value as a method for metabolic monitoring. REFERENCES Broder, G. and WeiI. M.H. (1964) Excess lactate: An index of reversibility of shock in human patients. Science, 143, 1457-1459. Cohen, R.D. and Simpson, R. (1975) Lactate metabolism. Anesthesiology, 43,661-673. Gallitz, T. Sandel, P., Jahmiirker, H., Rackwitz, R. and Haider, M. (19751 Ein prognostischer Index bei akutem Myokardinfarkt. Dtsch. Med. Wochenschr., 100,2517-2523. Jahrmlrker, H., Halbritter, R., Haider, M and Rackwitx, R. (1981) Prognostik und prognostische Parameter als Grundlage therapeutischer Entscheidungen in der Intensivmedixin. Internist, 22, 131-149. Kiinigshausen, Th., Hein, D., Schnurr, E. and Grabensee, B. (1978) Liquor-Lactat und Elektroenxephalogramm bei komat&en Patienten im Rahmen interner Krankheitsbilder. Dtsch. Med. Wochenschr., 103,99%1006. Levy, R., Elo, T. and Hanenson, I.B. (1977) Intravenous fructose treatment of acute alcohol intoxication. Arch. Intern. Med., 137, 117-&1177. Peretz, D.I., McGregor M. and Doesetor, J.B. (1964) Lactic acidosis: A clinically significant aspect of shock. Can. Med. Assoc. J.. 90,673+75.
146 Peretz, D.I., Scott, H.M., Duff, J., Dossetor, J.B., MacLean, L.D. and MacGregor, M. (19651 The significance of lacticacidemia in the shock syndrome. Ann. N.Y. Acad. Sci. 119, 1133-1141. Perret, C., Enrico, J.F. And Poli, S. (1970/71) Acid-base disturbances and lactate metabolism in shock (Abstract). Eur. J. Clin. Invest. 1, 387. Perret, C., Poli, S. and Enrico, J.F. (1969/701 Lactic acidosis and liver damage. Helv. Med. Ada, 35,377405. Rackwits, R., Jahrmiirker, H., Theisen, K., Halbritter, R., Otter, H.P. and Haider, M. (1975) Pathogenese und Therapie der Axidose bei Reanimation. Intensivmedizin, 12, l-23. Schiinbom, H., Kiimmerle, F. (1978) Die akute Pankreatitis und ihre Intensivtherapie. Intensivmedixin, 15, 39-44. Schuster, H.P., Kapp, S., Prellwitz, W., Schuster, C.J. and Weilemann L.S. (1981) Significance of hyperlactatemia in acute hypnotic drug poisoning. Klin. Woschenschr., 59, 599-605. Schuster, H.P., Prellwitz, W., Gunther, R., Kapp, S. and Weilemann, L.S. (1981) Verlaufsanalyse der Hyperlaktatiimie bei Patienten mit akuten Schlafmittelvergiftungen unterschiedlicher Schweregrade. Intensivmedizin, 18, 150-155. Vitek, V. and Cowley, R.A. (1971) Blood lactate in the prognosis of various forms of shock. Ann. Surg., 173, 308-313. Weil, M.H. and Afifi, A.A. (1970) Experimental and clinical studies of lactate and pyruvate as indicators of the severity of acute circulatory failure (Shock). Circulation, 41, 989-1001. von Wichert, P. and Bergengruen, 0. (1971) Laktat-Bestimmung im Blut. Med. Welt., 18, 752-756. Wright, N., Clarkson, A.R., Brown, S.S. and Fuster, V. (19711 Effects of poisoning on serum enzyme activities, Coagulation, and fibrinolysis. Br. Med. J., 3, 347350.