Intensive Care Med (1990) 16 [Suppl 3]:$243-$247 Intensive Care Medicine Springer-Verlag 1990 Treatment of sepsis in an intensive care unit C.C. Smith Department of Medicine, Aberdeen Royal Infirmaryand The InfectionUnit, City Hospital, Aberdeen, Scotland Abstract. The management of severe bacterial sepsis is an have a significantly higher mortality than do younger pa- integral part of intensive care medicine. Early and appro- tients [1]. This largely reflects an increased incidence of priate treatment with antimicrobials positively affects cardiovascular or pulmonary disease and major nutri- mortality and significantly reduces the time spent in both tional problems. The condition of the patient prior to ad- intensive care and the hospital. Drug choice is usually mission greatly influences the outcome following inten- made on a "best guess" basis and instituted prior to re- sive care management. Protracted shock with disseminat- ceipt of appropriate blood, sputum, urine or drainage ed intravascular coagulation (DIC) and renal failure with culture results. Bactericidal drugs should be given in com- acidaemia and hypoxaemia are associated with a high bination, delivered by intravenous bolus and directed to- mortality or protracted stay in ITU if they survive. Early wards broad cover of all likely pathogens. Aminoglyco- intervention is accompanied by an improved prognosis side/ureidopenicillin combinations are synergistic and [2, 3]. widely used - often combined with metronidazole. Once the patient is admitted to intensive care the risk Aminoglycoside toxicity can be reduced by giving the of developing nosocomial infection there will progressive- drug once daily (OD) rather than by traditional multiple ly increase the longer the patient remains in that environ- daily dosing (MDD) and by measuring peak and trough ment [4]. Oropharyngeal colonisation with potential serum levels. Efficacy is increased by attention to the (usually aerobic Gram-negative enteric derived) patho- peak serum level/MIC ratio which determines the re- gens is followed in a significant proportion of patients by sponse to treatment. Several newer agents have been more the development of pneumonia [5]. This may be compli- recently introduced. These drugs include ceftazidime, im- cated by bacteraemia and septic shock. These events are ipenem/cilastatin, the quinolones and clavulanic ac- particularly common in patients who require protracted id/semisynthetic penicillin combinations. Other newer ventilation (IPPV) [6]. Infection is therefore an impor- drugs currently under evaluation include aztreonam, tant limiting factor in the success of treatment delivered teicoplanin, the penems and carbapenems. in intensive care units and a frequent cause of the pa- tient's demise. For this reason early instigation of "best Key words: Severe infection - ITU setting - "best guess" intravenous bolus antimicrobial chemotherapy is guess" choice - Bactericidal antimicrobials - Combi- widely implemented [7]. Bactericidal drugs are delivered nations vs. monotherapy - Prevention of nosocomial in combination - and generally involve an aminoglyco- infection side with a ureidopenicillin - often combined with metronidazole. Antifungal and antiviral chemotherapy is occasionally also necessary, for example in immunocom- promised patients with systemic Candidiasis or CMV Infection is not infrequently the precipitant of admission pneumonia. to an intensive care unit from both the community and Newer drugs are coming forward for potential use in other services within the hospital. Septicaemic shock is intensive care, notably those which are broad-spectrum or most appropriately dealt with by the multidisciplinary safer than established antimicrobial~s. Ceftazidime [8] team approach in that environment. Most patients come and imipenem/cilastatin [9] have proved especially useful to intensive care after surgery - usually after major ab- following investigation and have been used as dominal and notably colorectal surgery. Others are ad- monotherapy. Other drugs currently under evaluation in- mitted following trauma or cardiopulmonary resuscita- clude aztreonam [10], the quinolones [11], penems and tion. All age groups are represented in intensive care - carbapenems. Aztreonam needs to be combined with an but the elderly with background disease and septic shock antimicrobial directed against Gram-positive pathogens $244 C.C. Smith: Treatment of severe sepsis because of its narrow Gram-negative spectrum of activity The patients in ITU [12]. Vancomycin remains a useful and widely employed drug while teicoplanin [13] is currently being assessed as A wide range of infections may precipitate septic shock a possible replacement for vancomycin and for potential and necessitate admission to an intensive care unit. Those use in "methicillin resistant" S. aureus (MRSA) infec- infections which are community-acquired include pneu- tions - which may become a problem in ITU's. Fluclox- monia caused by S. pneumoniae (notably type 3) and Kl. acillin, clavulanic acid/semisynthetic penicillin combina- pneumoniae with septicaemia, L. pneumophilia infection tions and several newer cephalosporins are used or are be- or post-influenzal S. aureus pneumonia in addition to ing evaluated in ITU's. The potential future usage of streptococcal and meningococcal infections with DIC. these drugs will be briefly developed in this overview of In-hospital transfer to the ITU is frequent after Gram- contemporary management of sepsis in intensive care. negative septicaemia - notably that due to E. coli, B. proteus, Enterobacter spp. or Ps. aeruginosa, especially when arising in elderly or compromised patients. Once patients have been admitted to the ITU environ- Diagnosis of sepsis ment they become liable to the development of secondary nosocomial infection [22], especially if they are being Early clinical diagnosis of "the sepsis syndrome" [3] and ventilated and their ITU stay exceeds four days. Most of rapid institution of appropriate antimicrobial and sup- the patients admitted have had recent surgery - notably portive treatment has long been known to significantly abdominal surgery, especially for colorectal disease, influence outcome [2]. The mortality from bacteraemia gastroduodenal or hepatobiliary problems, or major - both Gram-negative and Gram-positive, remains unac- trauma, and performed as an emergency with minimal ceptably high at over 20% in spite of the ready availabili- pre-operative preparation. These patients have a particu- ty of a wide range of effective drugs and access to inten- larly high incidence of Gram-negative and polymicrobial sive care in most major hospitals. If shock supervenes the sepsis and can only be appropriately managed in an ITU mortality rises to over 50~ [14]. It is therefore crucial setting. The likelihood of developing nosocomial pneu- that the clinical recognition of "the sepsis syndrome" be mia increases the longer the patient is there and receiving followed by early administration of bactericidal an- ventilation. These secondary infections may indeed lead timicrobials and appropriate supportive therapy to posi- to their demise. Preventive ploys are therefore being wide- tively influence progression of the condition [7]. The ly investigated and implemented to address this problem, longer the patient is bacteraemic or in shock the worse the most effective of which is selective decontamination the outcome. Development of the adult respiratory dis- of the gut [23], sometimes combined with parenterat an- tress syndrome (ARDS) necessitating ventilation is asso- timicrobial chemotherapy [24]. ciated with an increased stay in ITU and the potential for development of nosocomial infection - notably Gram- Established drugs negative pneumonia [15]. Long intravascular lines, in- dwelling bladder catheters and abdominal or thoracic The aminogIycosides are time-tested bactericidal an- drains further increase the potential for secondary infec- timicrobials which continue to occupy a central role in tion, often with "multi-resistant" Gram-negative bacteria the treatment of patients with severe bacterial infection and staphylococci [16, 171. Septicaemia, hypovolaemia, [25]. There are, however, gaps in their spectrum of activi- hypoxaemia, acidaemia and DIC with renal failure cre- ty (B. fragilis, Strep. pyogenes for example) and they ates problems with drug handling, especially if the pa- therefore are used as part of combination therapy. The tient is oliguric or receiving haemodialysis. This is espe- potential for nephrotoxicity and ototoxicity is consider- cially important with aminoglycoside therapy [18, 19]. able and the safety margin between efficacy and toxicity The potential for deleterious drug-induced sequelae is narrow [26]. Wide variation occurs in the half life of the obvious and, without regular measurement of peak and aminoglycosides in elderly patients, those with renal dys- trough levels, underdosing may result with significant de- function and even there where is apparently normal renal crease in the likelihood of successful treatment [20]. function [26, 27]. In some of these latter patients the half Objective bacteriological diagnosis should be at- life may be as long as 6-8 h. Regular monitoring of se- tempted in all patients prior to instigation of treatment rum peak and trough levels is therefore mandatory [28, by the taking of appropriate pre-treatment source cul- 291. The peak serum level should be taken one hour after tures in addition to aerobic and anaerobic blood cultures