key: cord-0006453-kp3880qr authors: Kumar, Ashir title: Septic shock—an update date: 1982 journal: Indian J Pediatr DOI: 10.1007/bf02752663 sha: 4a95d3997e23ff42216c2bfe5ce8e64b13fb4d2e doc_id: 6453 cord_uid: kp3880qr nan Shock is a descriptive term which in the critically ill patient indicates generalized inadequacy of perfusion to several major organ systems. Shock comprises of several signs and symptoms and is therefore a syndrome. ~!tis an acute process and patient usually dies without rapid and appropriate intervention. Recognition of patients at risk to gram negative infections and septicemia and the pathogenesis of shock enables one to establish the diagnosis early in the course of the syndrome and institute effective therapy. The early description of septic shock resulting from gram negative bacterial infection came from the observations of Waisbren and Spink. ~ The development and use of variety of antibiotics effective in the control of gram positive infections resulted in an increasing incidence of serious gram negative infections frequently complicated by septicemia3 The initiating factor in gram negative septicemia is endotoxin, a lipopolysaccharide which directly and in combination Pediatrics, Saint Luke'~ Hospital with other leukocytic components forms various vasoactive substances. Several gram positive organisms release exotoxin, which can act directly on the microvaseulature; teichoie acid of their cell walls also has endotoxin hke action. Septic shock can also result from certain virus, fungal, and rickettsial infections, s-6 Septic shock is accompanied by several pathophysioh,gical reactions which are mediated by enzymatic systems like, the coagulation cascade, immunologic factors and the direct action of endotoxin or teichoic acid on the vascular endothelium. These reactions result in: coagulation system activation and depletion of several coagulation factors, complement activation resulting in hypocomplementemia and lysosomal enzyme leaks, kinin system activation, Schwartzman phenomena resulting in both lysosome enzyme leak and diss~, minated intravascular coagulation, failure of micro-circulation resulting in tissue hypoxia, diffuse loss of plasma fluid proteins and loss of intravasculal" volume. This failure of micro-cirCulation if uncorrected leads to the development of severe acidosis. ~ Ar per se compromises the ability of~n~i~e circulation to adequately ~:~r~ontl anti eventually results in tissu~'Ja~,~o~ :da-tl death. Various theral~,Uti~ q~lim~tas are directed at inter~lhg~:J~ith ~Vb~ direct toxic effects #tr'~a~lo~o~ti~ o~,tmcular endothelium, I~ts .~01t~,,U~d~rrestii~g the progress of indiu ted by immunologidbph~liozmol~i~Joi~i~ Studies performed i~ piglets who have no antibody (Pig placenta being impermeable to maternal antibody), have shown that they develop septic shock due to gram negative endotoxins. ~ The direct effect, results in tissue injury, edema of vascular endothclium, and fever. Thus, both vascular damage and release of cell contents occur as a result of endotoxcmia. These changes lead to increased adhesiveness of vascular endothelium with adhesions of platelets OF SEPTIC SHOCK and activation of whole coagulation cascade. The swelling and the alterations in endothelium results in leakage of plasma from intravascular spaces thus resulting in hypovolemia and shock. A. Activation of complement system: Hageman Factor (Factor XI[) is directly activated by endotoxin which sets off the entire coagulation cascade through the generation of fibrin and leading to disseminated intravascular coagulation and depletion of various clotting factors. Endotoxin is capable of activating comlement pathways in two ways. The first requires the interaction of endotoxin with naturally occurring antibodies to gram negative bacteria, This chain of events initiates activation of all components of complement pathways .8 This complement activation occur in an uncontrolled fashion throughout the vascular space and the resulting active complement components are able to exert their physiological roles i e., platelet aggregation, increase m vascular permeability, activation of neutrophils with chemotactic migration and smooth muscle contraction. These events lead to toxic changes in the micro-circulation, tissue hypoxia, and metabolic acidosis. McCabe studied serum complement levels in bacteremia due to gram negative organismsP In the 41 patients with uncomplicated bacteremia the mean C3 levels (1515:51 mg/100ml) did not differ from the values in controls, however, a significant reduction in complement levels was observed in 26 patients with shock (105+31) and in the 19 patients who had a fatal outcome (984-38). McCabe concluded that the frequency of occurrence of shock or fatal outcome tended to parallel the degree of decrease ot r complement levels in serum specimens obtained shortly after the onset of baeteremia. Fenton and Strunk reported depressed levels of CH50, C3, C4, and factor B in three newborn infants with Group B streptococcal sepsis. 6 They demonstrated that in infants infected with Group B Streptococcus both alternative and direct complement pathways were activated, the complement and hematologic data and the Clinical course of these infants suggested lhat Group B Streptococcus has endotoxin-like properties which may explain the high mortality despite the prompt antibiotic therapy, e C. Activation of kallikrein and kinin system: Plasma kinins are biologicaly active peptides and are capable of a variety of physiologic events i. e, increased vascular permeability, smooth muscle relaxation, and hypotension, kinins are generally found in inactive precursors in certain cells and in the circulation. Kinins are activated by endotoxin through the intermediary effect of kallikrein as well as through the intermediation of natural antibody. 10 Thus kininis have a crucial role in the failure of micro-circulation resulting in tissue hypoxia and intractable metabolic acidosis. D. Antigen-Antibody Interaction : Antigen-antibody interaction between endotoxin in gram negative bacterial cell walls and natural antibodies result in activation of complement system, activation of the kinin system, and the Schwartzman reaction. Schwartzman reaction is associated with necrotizing effects on the vascular endothelium, platelet aggregation, and thrombosis which results in tissue hypoxia, metabolic acidosis and death. Schwartzman reaction also contributes to the release of lysosomal enzymes from cells. Release of lysosomal enzymes results in fluid leak, edema and tissue hypoxia. Waisbren and Spink in 1950 provided the classic description of a patienI ~I~"~ Z ~l~tOet;' t ~ They described ~4flde~'gl~S~ who seemed alert, but bltt~a'~'dete~table blood pressure, was able to respond to the questions but was unable to perform complex intellectual functions, had high temperatures with cold extremities and high pulse pressure. During the early stages of bacteremia when the patient "looks well" but is febrile and hypotensive the diagnosis is not often suspected and the valuable time is lost. Daring the course of the disease the patient may present with petechial or purpuric skin rash secondary to disseminated intravascular coagulopathy or may develop erythematous gangrenous areas of skin discoloration particularly around the mouth and nose. 4 Ihese sharply marginated circular purplish lesions are often associated with Pseudomonas or Serratia septicemia. Newborns and infants often present with hypotension and shock and early signs may not be apparent. A sequential approach in the management of child with septic shock is desirable (Table I ). The treatment plan described here is adapted from a publication by MEDCOM and concerning gram negative sepsis. 7 1. The first step is to quickly examine the child and establish the baseline data. Blood pressure, heart rate, and body temperature should be recorded. This examination may determine the severity of shock. 2. An airway should be provided, if patient is in need of one. Metabolic acidosis associated with m~cro-circulatory Vol. 49, No. 400 3. Central venous pressure should be recorded, this could be difficult to achieve in a newborn or an infant. Blood gases, electrolytes, blood urea nitrogen, and serum creatinine should also be obtained. Fibrin split products, platelet count, and careful examination of peripheral smear helps ',n evaluation of disseminated intravascular coagulation. The effective therapy for the expansion of vascular volume is administration of whole blood, plasma, isotonic saline solution or human serum albumin. Whole blood is preferable to packed cells because that expands plasma volume. Whole fresh blood can also provide some of the labile clotting factors. 5 4. Strict record of fluid intake and urine output has to be maintained. Urine output should be recorded on an hourly basis following catheterization. Catheterization should be done under aseptic conditions and connected to a dosed collecting system. Administration of intravenous fluids will be guided by urine output. If there is a decrease in the urine output a diagnosis of acute tubular necrosis should be considered. A rapid acting diuretic-like furosemide (2-4 rag/ kg) helps in "flushing" the renal tubules and prevents protein precipitation and augmentation of the disease process. 5. Appropriate cultures (both bacterial and viral) should be obtained. If the patient has received any prior antibiotic therapy the microbiology laboratory should be alerted. The cultures should be appropriately processed for isoFation of anaerobic organisms. Depending on ttle patient's age and suspecting microorganisms, appropriate antibiotics should be administered. Most of the antibiotics in high doses provide significant amount of sodium or potassium ions; this load may become very crucial if patient is in renal failure and is unable to excrete these ions. Creatinine clearance should be monitored as almost all aminogtycosides which are used frequently irt gram negative shock have renal toxicity. Cephalosporins and Moxalactam are not particularly toxic to kidney. If available serum levels of antibiotics should be obtained to monitor the dose and frequency of administration. 6. The use of a massive dose of glucocorticoid in endotoxemic shock remains controversial, ix Some controlled clinical studies have shown favorable effects of massive doses of corticosteroids on morbidity and mortality in septic shock while many others have not. ti It is speculated that the syndrome of septic shock represents the combined effects of several of the inflammatory systems already rally activated. Sheagren believes that therapy directed at inhibiting these systems at a very early stage may result in a significant decrease in mortality. 11 In septic shock various inflammatory processes, which are responsible for the body's defence against the microorganism, when activated results in shock producing inflammatory intravascular sequelae of bacteremia. Thus, the well-known adverse effects of glucocorticoids on tissue may be able to ameliorate the process and prevent the development of shock. 11 Complement pathways leading to endothelial cell damage are inhibited by high concentrations of steroids, aa' 14 Sibbald, et al recently demonstrated a decrease in capillary leakage after a large dose of glucocorticoids, is The patients who did not respond to glucocorticoids had leaky capillaries before the dose was adminitered, indicating that steroids can only influence the course if given in large doses early in the stage. Recently, Tiengo reported significant improvement after the administration of 0.0I mg/kg of naloxone in an eight year old child with meningococeal infection and septic shock) 6 Recent observation of Sibbald et al, that the endorphin system is involved in early stages of septic shock suggest that glucocorticoids should be helpful if administered early. 1s'17 These speculations are based on the fact that beta-lipoprotein, the precursors of beta endorphin originate from the same molecule as ACTH and as large amount ofglucoeorticoids would be expected to inhibit the release of ACTH, probably the release of endorphin eo,tld also be prevented by early administration of large doses of glucocorticoids, is Some physicians are now routinely using large doses of glucocortieoids in patients suspected of being in the early stages of septic shock, However, that judgement is not always easy, especially in a newborn and an infant. Clearly more data is needed in this area. If steroids are used they should be used only for a brief period (36-48 hrs). Exchange transfusion should be considered in the management of disseminated intravascular coagulation secondary to septicemia. Spink WW: A clinical appraisal of neomycin Changing ecology of bacterial infections as related to antibacterial therapy Gram negative septic shock Case Records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises Hodes HL : Care of the critically ill child : Endotoxin shock Complement activation and Group B Streptococcal infection in the newborn : Similarities to endotoxin shock Gram-negative bacterial endotoxins in gram negative sepsis Activation of the properdin pathway of complement in patients with gramnegative bacteremia Serum complement levels in bacteremia due to gram-negative organisms Plasma kallikrein and hageman factor in gram-negative bacteremia Septic shock and corticosteroids Clinical trial design in studies of corticosteroids for bacterial infections Corticosteroids inhibit complement.induced granulocyte aggregation : a possible mechanism for their efficacy in shock states Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro Alveocapillary permeability in human septic ARDS : Effect of high dose corticosteroid therapy Naloxone in irreversible shock Pressor effect of naloxone in septic shock Common precursor to corticotropins ard erdorphins