Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Septic Shock H. Delooz To cite this article: H. Delooz (1975) Septic Shock, Acta Clinica Belgica, 30:3, 236-240, DOI: 10.1080/17843286.1975.11717003 To link to this article: https://doi.org/10.1080/17843286.1975.11717003
Published online: 21 May 2016.
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236 CURRENT THERAPY
SEPTIC SHOCK
H. DELOOZ*
Shock, being a condition of inadequate tissue perfusion can be caused by an infectious process and is then called septic shock. Gram-negative as well as Gram-positive bacteria can cause sept!c shock. The toxins liberated by the bacteria, be they endotoxins or exotoxins , play a role in causing the shock but the bacterial invasion itself also appears to be an important element (11, 26). Why circulating bacteria and/or toxins cause shock in certain cases and not in others still remains an unanswered question. Another problem in connection with septic shock is the observation of two types of shock: a hyperdynamic form of shock, characterized by a normal to high cardiac output and normal to low peripheral resistance, and a hypodynamic form of shock, characterized by diminished cardiac output and increased peripheral resistance. Studies which attempted to prove a relationship between the Gram-staining of the causative agents and the type of shock were only partly successful (17, 28). Motin and co-workers think that once the complicating factor of hypovolaemia is excluded, Gram-negative bacteria cause hyperdynamic shock and Gram-positive bacteria cause hypodynamic shock. Another hypothesis considers the hyperdynamic and hypodynamic forms as two stages in the development of septic shock. The transition from one form to the other could then be caused by exhaustion of the myocardium , by inadequacy of the cellular metabolism * Spoedgevallendienst en Dienst An aesthesiologie, A.Z. Sint-Rafael, Leuven. Acta Clinica Belgica, 30, 3 (1975)
causing rupture of the lysosomal structure with liberation of enzymes and form ation of myocardial depressing factors (8), or else by a direct toxic influence on the myocardium . In fact even in the hyperdynamic phase of shock a cer~ tain degree of myocardial failure can be demonstrated as a flattened cardiac performance curve (29). It is interesting to note that the prog. nosis of septic shock correlates with the cardiac output (19) and that even hyperdynamic shock is accompanied by ineffecti~e tissue perfusion. Two conclusions can be drawn from this know. ledge: 1. If the hyperdynamic form and the hypodynamic form are two phases in the develop. ment of septic shock , an early diagnosis is of major importance as regards the prognosis, and 2. Unlike hypovolaemic and cardiogenic shock it is not the haemodynamic failure which is the primary factor in septic shock, which means that the cause of the inadequate tissue perfusion must lie at the level of the microcirculation or at the level of the cell mass itself. The mechanism by which the cellular disturbance develops is still unknown but there may be several contributing factors: I. Hypoxaemia is a constant phenomenon even during the early stages of septic shock. This hypoxaemia is only apparent in real septic shock and cannot be produced by the infusion of endotoxins alone (18). There may be a relationship between the hypoxaemia and the migration of throm-
SEPTIC SHOCK
2.
3.
4.
5.
6.
bocytes to the lungs during septic shock (15). The thrombocytes could liberate vasoactive products which cause hypoxaemia by th eir influence on the lung circulation. The autonomic nervous system may also play a role in the development of pulmonary pathology during septic shock (16). The cellular hypoxia may be enh anced by the so-called chemical shunt , caused by the increased affinity of hae moglobulin for oxygen following the diminished 2,3 DPG content of the erythrocytes in septic shock (13). Nevertheless cellular hypoxia by itself ca nnot explain the cellular failure in septic shock, since the changes found in the ultrastructure of hepatic cells in septic shock are not the same as ·those observed during hypoxia (27). A possible hypothesis is that an important part of the perhaps increased cardiac output is going to the infected part of the body. In favour of this hypothesis is the observation in dogs that a hyperdynamic form of shock only develops when ~n area of infection is present and not as the consequence of an infusion of endotoxins. A direct toxic influence on the cells from the toxins and possibly other toxic agents formed in the presence of the infection , is another hypothesis (3). Finally, Mel a and co-workers (I 4) think th at the presence of the bacteria causes the formation of a "membrane toxin" hav ing its influence on the capillary membrane as well as on the cell membranes and intracellular membranes, such as the lysosomal membranes. That such a process is initiated by an antigen-antibody reaction as was originally proposed by Spink (24, 25) is not yet proven, although Robin (20) observed a fall in the level of complement in septic shock whereas no such fall was seen in sepsis without shock or in shock without sepsis. The most important factor in the course of septic shock, remains the threat to the periphery existing even before haemodynamic failure
237 appea rs. If during the evolution of the septic shock dec reased cardiac outpu t develops, insult will be add ed to injury as far as th e cells are co ncerned. The diagnosis of se ptic shock must be made on a clinical basis. Two symptoms which should arouse suspicion if present during the course of infection are: I. Mental confusion , depress ion or disorientation, and 2. A low arterial p0 2. The diagnosis will be confirmed by : I. Meas urement of the arterial press ure. A systolic pressure below 90 mm Hg wi ll always be found. Only by measuring th e arteri al pressure can th e diagnosis be made, for palpation of the pulse will often reveal forceful pulsations especiall y in the hyperdynamic form of septic shock . 2. The presence of oliguria or an uria. Catheterization of the bladder and observation of th e diuresis after ernptying the bladder is necessary. Fever and shivering may be present but are not essential for diagnosis of septic shock. The therapeutic scheme which we propose is based on 5 principles: I. Early diagnosis. 2. Elimination of every possible degree of hypovolaem ia. 3. Antibiotics and corticoids. 4. Positive inotropic agents if a cardiac component in the failing tissue perfusion is suspected. 5. Aggressive surgery if necessary and as soon as the condition of shock has been reversed. The steps to be followed in the th erapy of septic shock are as follows : I. Early diagnosis by measuring the arterial pressure, determining arterial blood gases and observation of the diuresis. 2. Liberal administration of oxygen. However when the patient has a history of chronic C02-retention, oxygen therapy should be started with caution. 3. Positioning of a central venous catheter. The central venous pressure is evaluated and blood samples are taken for the determinaActa C/inica Be/gica, 30, 3 (1975)
238 tion of hae matocrit , biochemistry and clotting tests. Hae mocultures are started and the Limulus-test is performed when possible (9). 4. Samples are taken from sputum , urine and possibl y from wounds and drainages for culture and determination of the senti vit y to an tibibtics. 5. The central venous pressure is raised to 10 em of water to eliminate any concomitant hypovolaemia. Since an increased capillary permeability is present in septic shock, solutions employed to raise the circulating volume should be chosen taking this factor into accou nt. If the haematocrit is below 35% blood will be used, if the hae matocrit is 35 % or higher solutions of human albumin or low molecular weight dextran are used. At the same time every deviation of normal acid base eq uilibrium is corrected and artificial ventilation is started when indicated by the results of the blood gas determinations or by clinical observation . 6. Broad spectrum antibiotics are intravenously administered in high doses even in the presence of anuria. Only the subsequent dosages will be adapted according to the renal function. 7. Together with the antibiotics, corticosteroids are administered in a dose corresponding to 30 mg of prednisolone per kg body ~ e i g ht. The corticosteroids are injected slowl y intravenously over a period of 10 minutes. Only if the shock symptoms persist need the corti costeroid administration be repeated. This may be necessary about 2 to 6 hours after the first corticosteroid administration . The central venous pressure has to be monitored continuously and has to be kept at 10 em of water by adapting the speed of infusion of the liquids mentioned under 6. As far as the indications for the use of corticosteroids are concerned several arguments can be put forward: l) they have a positive haemodynamic effect by increasing the cardiac output and decreasing the peripheral resistance (10, II); Acta Clinica Be/gica, 30. 3 (1975)
SEPTIC SHOCK
2) th ey have a positive metabolic effect: the metaboli m of lactic acid is increased and the amoun t of circulating free fatt y ac ids and amino acids is reduced (22); 3) they have a protective effect on the lysoso mal structures (5, 6); 4) th ey decrease the prod ucti on of myocardial depres.sant factor (8); 5) they interfere in a negati ve way with the sy mpathetic nerve transmission (2); 6) they protect aga inst possible immu ne reacti on initiated by the infectious process (23); 7) they have a positive influence on tissue p0 1 and pC0 1 (21 ); 8) th ey restore the 2,3 DPG concentration of the erythrocytes (13). All these effects plead in favour of the ad ministration of corticosteroids but especiall y of the earl y administration of corticosteroids. Of course, the administration of corticosteroids has to be accompanied by all the other therapeutic measures mentioned before. 8. The ad ministration of digitalis intrave nously is indicated to prevent or reverse the complicating myocardial failure (4) which usually appears in the evolution of the septic shock syndrome (29). 9. If tissue perfusion remains inadequate we must accept that an important myocardial failure factor is complicating the picture and the use of dru gs that increase myoca rdial contractility must be started. Our preference is for dopamine, a natural precursor of noradrenaline, because it is characterized by a positive effect on myocardial contractility coupled with a mild chronotropic effect and a selective vasodilatory effect on the kidneys and the splanchnic area (12 , 29). These properties of dopamine however are only witnessed when a low dose of the drug is used, higher doses will cause a general vasoconstriction . Therefore the administration must be started with 1 to 2 micrograms per kg body weight and per minute. The doses can be increased by steps of 2 micro-
SEPTIC SHOCK
grams up to a maximum of 12 to 16 micrograms per kg and per minute. 10. Signs of intravascular clotting are frequently seen in septic shock, and the question may be _ raised . whether the administration of heparin should not be routine. We do not include this therapeutic step in our scheme because frequently surgery may be needed as soon as the shock condition is reversed and our experience, as well as th at of other investigators (1), indicates that the most important goal remains reversion of the shock, for as soon as adequate tissue perfusion is restored the clotting factors will return to normal without any specific therapy. To conclude, we want to stress that the therapy of septic shock requires the application of all the different steps outlined in our therapeutic scheme. If the quality of the therapeutic steps is important, a rapid succession of these steps is of even greater importance. Of course the success of the proposed therapeutic scheme will depend largely on the possibility of applying it in a controlled situation which requires the facilities necessary for the treatment of the critically ill and the continuous presence at the bedside of a doctor trained in critical care medicine. Finally, it must be borne in mind that the therapeutic scheme may, quite often, have only a symptomatic value which means that the ultimate outcome of the underlying disease will very often depend on the application of aggressive surgery as soon as possible (7). REFERENCES I. CORRIGAN, J.J ., JORDAN, C.M., BENNETT, B.B." Disseminated intravascular coagulati on in septic shock". Am. J. Dis. Child., 126. 629,1973 . 2. DIETZMAN , R.H.- "The influence of the sympath etic nervous system upon survi val in ex perimental cardiogenic and endotoxic shock ". Thesis Ph. D., Universi ty of Minnesota Health Center, 1972. 3. DUFF, J.H., WRIGHT, C.J. , MACLEAN , A.P.H., MACLEAN, L.D. - "Oxygen consumption in septic shock ". in Forscher B.K ., Lillehei R.C., Stubbs S.S. " Shock in low- and high-flow states " . Excerpra Medica. Amsterdam, p. 235-239, 1972. 4. HINSHAW, L.B., ARC HER, L.T. , BLACK , M.R.,
239 GR EENFIELD , L.J ., GUENTER, C.A.- " Preve ntion and reversa l of myocardi al fail ure in endotox in shock" . Surgery, Gynec. and Obsrer. , /36, I, 1973. 5. JANOFF, A., WEISSMAN , G., ZWE IFACH. B.W., THOMAS, L. -" Path ogenesis of expe rime ntal shock , studies on lysoso mes in normal and tolerant animals subjected to lethal traum a and endotoxemia ". J. Exp. Med., 116, 45 1, 1962 . 6. JANOFF, A. -" Alterati ons in lysosomes (intracellular enzy mes) during shock: effects of preco nditioning (tolerance) and protective drugs". in Hershey S.G. "Shock", Little, Brown and Company, Boston (1 964), p. 93-112 . 7. LEDINGHAM , I MCA, McARDLE, C.S., FISH ER, W.O., MADDERN , M., MACDONALD , J.A.E., MILLIGAN , G.F. , MELLON , A., WADD ELL, G., SCOTT, P.D.R., LEES, N.W. - "A prospective clinical study of se ptic shock" . First World Congress on Intensive Care, London 1974. 8. LEFER , A.M. -" Role of a myocardi al depressant fac tor in th e pathogenesis of circulatory shock". Fed. Proc .. 29, 1836, 1970. 9. LEVIN , J. , BAUG , F.B.- " The role of endotoxi n in th e extracellularcoagulation ofLimulus blood" . Bull. John's Hopkins Hosp., 115, 265 , 1964. 10. LILLEHEI , R.C. , LONG ERB EA M, J.K., BLOCK, J.H., MANAX, W.O. - " The nature of irreversible shoc k; ex perimental and clinical observations". Ann. Surg., /60, 682, 1964. II. LILLEHEI , R.C., MOTSAY , GJ. , SCHULTZ, C. H."Experimental and clinical effects of methylprednisolone used in the prevention and treatment of traumati c, se ptic shock". First World Congress on Intensive Care, London, 1974. 12. MACCONNELL, K.L. , McNAY , J.L., MEY ER, M.B., GOLDBERG, L.l. - "Dopamine in the treatm ent of hypotension and shock". New England J. M ed. , 275, 1389, 1966. 13. McCONN , R. - "2.3-DPG. What role in septic shock?" in Forscher B.K., Lillehei R.C. , Stubbs S.S. " Shock in low- and high-fl ow states". Exerpta Media , Amsterdam (1972), p. 28-41. 14. MELA, L. , MILLER, L.D., BACALZO , L.V . Jr. , OLOFSSON. K., WHITE , R.R.- " Role of intracellular variations of lysosomal enzyme activity and oxygen tension in mitoc hond ri al impairment in endotoxemia and hemorrh age in the rat ". Ann. Surg. , 178, 727, 1973. 15. MILLIGAN , G.F., MACDONALD, J.A.E., MELLON, A., LEDINGHAM, I. MeA - "Pulmonary and hematologic disturbances during septic shock". Surg., Gynec., Obster.. /38, 43 , 1974. 16. MOSS, G , STAUNTON , C., STE IN , A.A. - "Cereb ral hypox ia a th e primary even t in th e pathogenesis of th e " Shock lung sy ndrome". Surg. Forum . 22 , 211 , 197 1. 17. MOTIN , J., BO ULETREAU . P , PET IT. P.. LA TARJET, J. - " Hae modyn amic stud y of septic shock" . First World Congress on Intensive Care, London. 1974. 18. MOTSAY, G.J .. DIETZMAN , R.H., SCHULTZ, L.S., Acta C/inica Belgica, 30, 3 (1975)
240 ROMERO, L.H., LILLEHEI, R.C. - "EfTects of massive doses of corticosteroids in experimental and clinical Gram-negative septic shock ". in Forscher B.K., Lillehei, R.C., Stubbs S.S. " Shock in low- and high-flow states". Exerpta Medica, Amsterdam (1972), p. 292-304. 19. NISHIJIMA , H., SHUBIN, H., CAVAMILLES, J., WElL, M.H. - "Shock associated with Gram-negative vaeseraemia" FirSt World Congress on Intensive Care, London , 1974. 20. ROBIN, M., INTRA TOR, L. , RAPIN, M. - "Complement activation during human septic shock". First World Congress on Intensive Care, London 1974. 21. ROSENBAUM , R.W., HAYES, M.F., MATSUMOTO , T. - "Efficacy of steroids in the treatment of septic and cardiogenic shock". Surg., Gynec.. Obstet., 136, 914, 1973. 22. SCHUMER, W., NYHUS, L.M . - "The role of corti coids in the manage ment . of shock ". Surg. Clin. N. Amer., 49, 147, 1969. 23. SCHUMER, W., ERVE, P.R. , OBERNOLTE, R.P. " Mechanisms of steroid protection in septic shock ". Surgery, 72, 119, 1972.
.Acta Cl/nica Belgica, 30, 3 (1975)
SEPTIC SHOCK
24. SPINK, W.W., BRANDE. A.l., CASTENADA , M.R., GOYTIA , R.S.- "A ureomycin therapy in human bru cellosis due to Brucella melitensis" . J. A mer. M ed. Ass. , / 38, 1145, 1948. 25 . SPINK, W.W.- " The role of endotoxin in shock" in Forscher B.K. , Lillehei R.C., Stubbs S.S. "Shock in low. and high-now states" . Excerpta Medica, Amsterdam (1972), p. 226-229. 26. THAL, A.P. - "Shock, a physiologic basis for treatment " . Year Book Medical Publishers Inc., Chicago, 1971. 27. WHITE, R.R., MELA , L. , BACALZO, L.V . Jr., OLOFSSON, K., MILLER, L.D. - " Hepatic ultrastructure in endotoxemia, hemorrhage and hypoxia: emphasis on mitochondrial changes". Surgery, 73, 525, 1973. 28. WILSON, R.F., CHISCANO, A.D., QUADROS, E., TARV ER, M. -"Some observations.on 132 patients with septic shock" . A nesth . Ana/g. (Cleveland), 46, 75 I, 1967. 29. WINSLOW, E.J., LOEB, H.S., RAHIMTOOLA , S.H ., KAMTH, S., GUNNAR , R.M.- " Hemod ynamic studies and results of therapy in 50 patients with bacteremic shock " . A m. J. Mecl.. 54, 421, 1973.
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Septic Shock H. Delooz To cite this article: H. Delooz (1975) Septic Shock, Acta Clinica Belgica, 30:3, 236-240, DOI: 10.1080/17843286.1975.11717003 To link to this article: https://doi.org/10.1080/17843286.1975.11717003
Published online: 21 May 2016.
Submit your article to this journal
Article views: 1
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20
236 CURRENT THERAPY
SEPTIC SHOCK
H. DELOOZ*
Shock, being a condition of inadequate tissue perfusion can be caused by an infectious process and is then called septic shock. Gram-negative as well as Gram-positive bacteria can cause sept!c shock. The toxins liberated by the bacteria, be they endotoxins or exotoxins , play a role in causing the shock but the bacterial invasion itself also appears to be an important element (11, 26). Why circulating bacteria and/or toxins cause shock in certain cases and not in others still remains an unanswered question. Another problem in connection with septic shock is the observation of two types of shock: a hyperdynamic form of shock, characterized by a normal to high cardiac output and normal to low peripheral resistance, and a hypodynamic form of shock, characterized by diminished cardiac output and increased peripheral resistance. Studies which attempted to prove a relationship between the Gram-staining of the causative agents and the type of shock were only partly successful (17, 28). Motin and co-workers think that once the complicating factor of hypovolaemia is excluded, Gram-negative bacteria cause hyperdynamic shock and Gram-positive bacteria cause hypodynamic shock. Another hypothesis considers the hyperdynamic and hypodynamic forms as two stages in the development of septic shock. The transition from one form to the other could then be caused by exhaustion of the myocardium , by inadequacy of the cellular metabolism * Spoedgevallendienst en Dienst An aesthesiologie, A.Z. Sint-Rafael, Leuven. Acta Clinica Belgica, 30, 3 (1975)
causing rupture of the lysosomal structure with liberation of enzymes and form ation of myocardial depressing factors (8), or else by a direct toxic influence on the myocardium . In fact even in the hyperdynamic phase of shock a cer~ tain degree of myocardial failure can be demonstrated as a flattened cardiac performance curve (29). It is interesting to note that the prog. nosis of septic shock correlates with the cardiac output (19) and that even hyperdynamic shock is accompanied by ineffecti~e tissue perfusion. Two conclusions can be drawn from this know. ledge: 1. If the hyperdynamic form and the hypodynamic form are two phases in the develop. ment of septic shock , an early diagnosis is of major importance as regards the prognosis, and 2. Unlike hypovolaemic and cardiogenic shock it is not the haemodynamic failure which is the primary factor in septic shock, which means that the cause of the inadequate tissue perfusion must lie at the level of the microcirculation or at the level of the cell mass itself. The mechanism by which the cellular disturbance develops is still unknown but there may be several contributing factors: I. Hypoxaemia is a constant phenomenon even during the early stages of septic shock. This hypoxaemia is only apparent in real septic shock and cannot be produced by the infusion of endotoxins alone (18). There may be a relationship between the hypoxaemia and the migration of throm-
SEPTIC SHOCK
2.
3.
4.
5.
6.
bocytes to the lungs during septic shock (15). The thrombocytes could liberate vasoactive products which cause hypoxaemia by th eir influence on the lung circulation. The autonomic nervous system may also play a role in the development of pulmonary pathology during septic shock (16). The cellular hypoxia may be enh anced by the so-called chemical shunt , caused by the increased affinity of hae moglobulin for oxygen following the diminished 2,3 DPG content of the erythrocytes in septic shock (13). Nevertheless cellular hypoxia by itself ca nnot explain the cellular failure in septic shock, since the changes found in the ultrastructure of hepatic cells in septic shock are not the same as ·those observed during hypoxia (27). A possible hypothesis is that an important part of the perhaps increased cardiac output is going to the infected part of the body. In favour of this hypothesis is the observation in dogs that a hyperdynamic form of shock only develops when ~n area of infection is present and not as the consequence of an infusion of endotoxins. A direct toxic influence on the cells from the toxins and possibly other toxic agents formed in the presence of the infection , is another hypothesis (3). Finally, Mel a and co-workers (I 4) think th at the presence of the bacteria causes the formation of a "membrane toxin" hav ing its influence on the capillary membrane as well as on the cell membranes and intracellular membranes, such as the lysosomal membranes. That such a process is initiated by an antigen-antibody reaction as was originally proposed by Spink (24, 25) is not yet proven, although Robin (20) observed a fall in the level of complement in septic shock whereas no such fall was seen in sepsis without shock or in shock without sepsis. The most important factor in the course of septic shock, remains the threat to the periphery existing even before haemodynamic failure
237 appea rs. If during the evolution of the septic shock dec reased cardiac outpu t develops, insult will be add ed to injury as far as th e cells are co ncerned. The diagnosis of se ptic shock must be made on a clinical basis. Two symptoms which should arouse suspicion if present during the course of infection are: I. Mental confusion , depress ion or disorientation, and 2. A low arterial p0 2. The diagnosis will be confirmed by : I. Meas urement of the arterial press ure. A systolic pressure below 90 mm Hg wi ll always be found. Only by measuring th e arteri al pressure can th e diagnosis be made, for palpation of the pulse will often reveal forceful pulsations especiall y in the hyperdynamic form of septic shock . 2. The presence of oliguria or an uria. Catheterization of the bladder and observation of th e diuresis after ernptying the bladder is necessary. Fever and shivering may be present but are not essential for diagnosis of septic shock. The therapeutic scheme which we propose is based on 5 principles: I. Early diagnosis. 2. Elimination of every possible degree of hypovolaem ia. 3. Antibiotics and corticoids. 4. Positive inotropic agents if a cardiac component in the failing tissue perfusion is suspected. 5. Aggressive surgery if necessary and as soon as the condition of shock has been reversed. The steps to be followed in the th erapy of septic shock are as follows : I. Early diagnosis by measuring the arterial pressure, determining arterial blood gases and observation of the diuresis. 2. Liberal administration of oxygen. However when the patient has a history of chronic C02-retention, oxygen therapy should be started with caution. 3. Positioning of a central venous catheter. The central venous pressure is evaluated and blood samples are taken for the determinaActa C/inica Be/gica, 30, 3 (1975)
238 tion of hae matocrit , biochemistry and clotting tests. Hae mocultures are started and the Limulus-test is performed when possible (9). 4. Samples are taken from sputum , urine and possibl y from wounds and drainages for culture and determination of the senti vit y to an tibibtics. 5. The central venous pressure is raised to 10 em of water to eliminate any concomitant hypovolaemia. Since an increased capillary permeability is present in septic shock, solutions employed to raise the circulating volume should be chosen taking this factor into accou nt. If the haematocrit is below 35% blood will be used, if the hae matocrit is 35 % or higher solutions of human albumin or low molecular weight dextran are used. At the same time every deviation of normal acid base eq uilibrium is corrected and artificial ventilation is started when indicated by the results of the blood gas determinations or by clinical observation . 6. Broad spectrum antibiotics are intravenously administered in high doses even in the presence of anuria. Only the subsequent dosages will be adapted according to the renal function. 7. Together with the antibiotics, corticosteroids are administered in a dose corresponding to 30 mg of prednisolone per kg body ~ e i g ht. The corticosteroids are injected slowl y intravenously over a period of 10 minutes. Only if the shock symptoms persist need the corti costeroid administration be repeated. This may be necessary about 2 to 6 hours after the first corticosteroid administration . The central venous pressure has to be monitored continuously and has to be kept at 10 em of water by adapting the speed of infusion of the liquids mentioned under 6. As far as the indications for the use of corticosteroids are concerned several arguments can be put forward: l) they have a positive haemodynamic effect by increasing the cardiac output and decreasing the peripheral resistance (10, II); Acta Clinica Be/gica, 30. 3 (1975)
SEPTIC SHOCK
2) th ey have a positive metabolic effect: the metaboli m of lactic acid is increased and the amoun t of circulating free fatt y ac ids and amino acids is reduced (22); 3) they have a protective effect on the lysoso mal structures (5, 6); 4) th ey decrease the prod ucti on of myocardial depres.sant factor (8); 5) they interfere in a negati ve way with the sy mpathetic nerve transmission (2); 6) they protect aga inst possible immu ne reacti on initiated by the infectious process (23); 7) they have a positive influence on tissue p0 1 and pC0 1 (21 ); 8) th ey restore the 2,3 DPG concentration of the erythrocytes (13). All these effects plead in favour of the ad ministration of corticosteroids but especiall y of the earl y administration of corticosteroids. Of course, the administration of corticosteroids has to be accompanied by all the other therapeutic measures mentioned before. 8. The ad ministration of digitalis intrave nously is indicated to prevent or reverse the complicating myocardial failure (4) which usually appears in the evolution of the septic shock syndrome (29). 9. If tissue perfusion remains inadequate we must accept that an important myocardial failure factor is complicating the picture and the use of dru gs that increase myoca rdial contractility must be started. Our preference is for dopamine, a natural precursor of noradrenaline, because it is characterized by a positive effect on myocardial contractility coupled with a mild chronotropic effect and a selective vasodilatory effect on the kidneys and the splanchnic area (12 , 29). These properties of dopamine however are only witnessed when a low dose of the drug is used, higher doses will cause a general vasoconstriction . Therefore the administration must be started with 1 to 2 micrograms per kg body weight and per minute. The doses can be increased by steps of 2 micro-
SEPTIC SHOCK
grams up to a maximum of 12 to 16 micrograms per kg and per minute. 10. Signs of intravascular clotting are frequently seen in septic shock, and the question may be _ raised . whether the administration of heparin should not be routine. We do not include this therapeutic step in our scheme because frequently surgery may be needed as soon as the shock condition is reversed and our experience, as well as th at of other investigators (1), indicates that the most important goal remains reversion of the shock, for as soon as adequate tissue perfusion is restored the clotting factors will return to normal without any specific therapy. To conclude, we want to stress that the therapy of septic shock requires the application of all the different steps outlined in our therapeutic scheme. If the quality of the therapeutic steps is important, a rapid succession of these steps is of even greater importance. Of course the success of the proposed therapeutic scheme will depend largely on the possibility of applying it in a controlled situation which requires the facilities necessary for the treatment of the critically ill and the continuous presence at the bedside of a doctor trained in critical care medicine. Finally, it must be borne in mind that the therapeutic scheme may, quite often, have only a symptomatic value which means that the ultimate outcome of the underlying disease will very often depend on the application of aggressive surgery as soon as possible (7). REFERENCES I. CORRIGAN, J.J ., JORDAN, C.M., BENNETT, B.B." Disseminated intravascular coagulati on in septic shock". Am. J. Dis. Child., 126. 629,1973 . 2. DIETZMAN , R.H.- "The influence of the sympath etic nervous system upon survi val in ex perimental cardiogenic and endotoxic shock ". Thesis Ph. D., Universi ty of Minnesota Health Center, 1972. 3. DUFF, J.H., WRIGHT, C.J. , MACLEAN , A.P.H., MACLEAN, L.D. - "Oxygen consumption in septic shock ". in Forscher B.K ., Lillehei R.C., Stubbs S.S. " Shock in low- and high-flow states " . Excerpra Medica. Amsterdam, p. 235-239, 1972. 4. HINSHAW, L.B., ARC HER, L.T. , BLACK , M.R.,
239 GR EENFIELD , L.J ., GUENTER, C.A.- " Preve ntion and reversa l of myocardi al fail ure in endotox in shock" . Surgery, Gynec. and Obsrer. , /36, I, 1973. 5. JANOFF, A., WEISSMAN , G., ZWE IFACH. B.W., THOMAS, L. -" Path ogenesis of expe rime ntal shock , studies on lysoso mes in normal and tolerant animals subjected to lethal traum a and endotoxemia ". J. Exp. Med., 116, 45 1, 1962 . 6. JANOFF, A. -" Alterati ons in lysosomes (intracellular enzy mes) during shock: effects of preco nditioning (tolerance) and protective drugs". in Hershey S.G. "Shock", Little, Brown and Company, Boston (1 964), p. 93-112 . 7. LEDINGHAM , I MCA, McARDLE, C.S., FISH ER, W.O., MADDERN , M., MACDONALD , J.A.E., MILLIGAN , G.F. , MELLON , A., WADD ELL, G., SCOTT, P.D.R., LEES, N.W. - "A prospective clinical study of se ptic shock" . First World Congress on Intensive Care, London 1974. 8. LEFER , A.M. -" Role of a myocardi al depressant fac tor in th e pathogenesis of circulatory shock". Fed. Proc .. 29, 1836, 1970. 9. LEVIN , J. , BAUG , F.B.- " The role of endotoxi n in th e extracellularcoagulation ofLimulus blood" . Bull. John's Hopkins Hosp., 115, 265 , 1964. 10. LILLEHEI , R.C. , LONG ERB EA M, J.K., BLOCK, J.H., MANAX, W.O. - " The nature of irreversible shoc k; ex perimental and clinical observations". Ann. Surg., /60, 682, 1964. II. LILLEHEI , R.C., MOTSAY , GJ. , SCHULTZ, C. H."Experimental and clinical effects of methylprednisolone used in the prevention and treatment of traumati c, se ptic shock". First World Congress on Intensive Care, London, 1974. 12. MACCONNELL, K.L. , McNAY , J.L., MEY ER, M.B., GOLDBERG, L.l. - "Dopamine in the treatm ent of hypotension and shock". New England J. M ed. , 275, 1389, 1966. 13. McCONN , R. - "2.3-DPG. What role in septic shock?" in Forscher B.K., Lillehei R.C. , Stubbs S.S. " Shock in low- and high-fl ow states". Exerpta Media , Amsterdam (1972), p. 28-41. 14. MELA, L. , MILLER, L.D., BACALZO , L.V . Jr. , OLOFSSON. K., WHITE , R.R.- " Role of intracellular variations of lysosomal enzyme activity and oxygen tension in mitoc hond ri al impairment in endotoxemia and hemorrh age in the rat ". Ann. Surg. , 178, 727, 1973. 15. MILLIGAN , G.F., MACDONALD, J.A.E., MELLON, A., LEDINGHAM, I. MeA - "Pulmonary and hematologic disturbances during septic shock". Surg., Gynec., Obster.. /38, 43 , 1974. 16. MOSS, G , STAUNTON , C., STE IN , A.A. - "Cereb ral hypox ia a th e primary even t in th e pathogenesis of th e " Shock lung sy ndrome". Surg. Forum . 22 , 211 , 197 1. 17. MOTIN , J., BO ULETREAU . P , PET IT. P.. LA TARJET, J. - " Hae modyn amic stud y of septic shock" . First World Congress on Intensive Care, London. 1974. 18. MOTSAY, G.J .. DIETZMAN , R.H., SCHULTZ, L.S., Acta C/inica Belgica, 30, 3 (1975)
240 ROMERO, L.H., LILLEHEI, R.C. - "EfTects of massive doses of corticosteroids in experimental and clinical Gram-negative septic shock ". in Forscher B.K., Lillehei, R.C., Stubbs S.S. " Shock in low- and high-flow states". Exerpta Medica, Amsterdam (1972), p. 292-304. 19. NISHIJIMA , H., SHUBIN, H., CAVAMILLES, J., WElL, M.H. - "Shock associated with Gram-negative vaeseraemia" FirSt World Congress on Intensive Care, London , 1974. 20. ROBIN, M., INTRA TOR, L. , RAPIN, M. - "Complement activation during human septic shock". First World Congress on Intensive Care, London 1974. 21. ROSENBAUM , R.W., HAYES, M.F., MATSUMOTO , T. - "Efficacy of steroids in the treatment of septic and cardiogenic shock". Surg., Gynec.. Obstet., 136, 914, 1973. 22. SCHUMER, W., NYHUS, L.M . - "The role of corti coids in the manage ment . of shock ". Surg. Clin. N. Amer., 49, 147, 1969. 23. SCHUMER, W., ERVE, P.R. , OBERNOLTE, R.P. " Mechanisms of steroid protection in septic shock ". Surgery, 72, 119, 1972.
.Acta Cl/nica Belgica, 30, 3 (1975)
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24. SPINK, W.W., BRANDE. A.l., CASTENADA , M.R., GOYTIA , R.S.- "A ureomycin therapy in human bru cellosis due to Brucella melitensis" . J. A mer. M ed. Ass. , / 38, 1145, 1948. 25 . SPINK, W.W.- " The role of endotoxin in shock" in Forscher B.K. , Lillehei R.C., Stubbs S.S. "Shock in low. and high-now states" . Excerpta Medica, Amsterdam (1972), p. 226-229. 26. THAL, A.P. - "Shock, a physiologic basis for treatment " . Year Book Medical Publishers Inc., Chicago, 1971. 27. WHITE, R.R., MELA , L. , BACALZO, L.V . Jr., OLOFSSON, K., MILLER, L.D. - " Hepatic ultrastructure in endotoxemia, hemorrhage and hypoxia: emphasis on mitochondrial changes". Surgery, 73, 525, 1973. 28. WILSON, R.F., CHISCANO, A.D., QUADROS, E., TARV ER, M. -"Some observations.on 132 patients with septic shock" . A nesth . Ana/g. (Cleveland), 46, 75 I, 1967. 29. WINSLOW, E.J., LOEB, H.S., RAHIMTOOLA , S.H ., KAMTH, S., GUNNAR , R.M.- " Hemod ynamic studies and results of therapy in 50 patients with bacteremic shock " . A m. J. Mecl.. 54, 421, 1973.
