Glenda J. Garvey

Practice Parameters for Evaluating New Fever in Critically Ill Adult Patients. Task Force of the American College of Critical Care Medicine of the Society of Critical Care Medicine in Collaboration with the Infectious Disease Society of America.

Abstract Objective: To develop practice parameters for the evaluation of adult patients who develop a new fever in the intensive care unit (ICU) for the purpose of guiding clinical practice. Participants: A task force of 13 experts in disciplines related to critical care medicine, infectious diseases, and surgery was convened from the membership of the Society of Critical Care Medicine, and the Infectious Disease Society of America. Evidence: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four categories, according to study design and scientific value. Consensus Process: The task force met several times in person and twice monthly by teleconference over a 1‐yr period of time to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the experts’ opinions. Draft documents were composed and debated by the task force until consensus was reached by nominal group process. Conclusions: The panel concluded that, because fever can have many infectious and noninfectious etiologies, a new fever in a patient in the ICU should trigger a careful clinical assessment rather than automatic orders for laboratory and radiologic tests. A cost‐conscious approach to obtaining cultures and imaging studies should be undertaken if it is indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether or not infection is present, so additional testing can be avoided and therapeutic options can be made. (Crit Care Med 1998; 26:392‐408) In some intensive care units (ICUs), the measurement of a newly elevated temperature triggers an automatic order set which includes many tests that are time consuming, costly, and disruptive (Table 1). Moreover, the patient may experience discomfort, be exposed to unneeded radiation, or experience considerable blood loss due to this testing, which is often repeated several times within 24 hrs, and daily thereafter. In an era when utilization of hospital and patient resources is under intensive scrutiny, it is appropriate to assess how such fevers should be evaluated in a prudent and cost‐effective manner. Table 1. Typical costs associated with fever evaluation The American College of Critical Care Medicine of the Society of Critical Care Medicine and the Infectious Disease Society of America established a Task Force to provide practice parameters for the evaluation of a new fever in patients in an ICU with the goal of promoting the rational consumption of resources and promoting an efficient evaluation. These practice parameters presume that any unexplained temperature elevation merits a clinical assessment by a healthcare professional that includes a review of the patients history and a focused physical examination before any laboratory tests or imaging procedures are ordered. These practice parameters specifically address how to evaluate a new fever in an adult patient already in the ICU who has previously been afebrile and in whom the source of fever is not initially obvious. If the initial evaluation of history and physical examination reveals a consolidated lung, a purulent wound, or a phlebitic leg, then diagnosis and therapy of that infectious process should commence: such management is addressed by other practice parameters aimed specifically at pneumonia, catheter‐related infections, etc. Specific questions addressed in these practice parameters relate to the search for the underlying cause of fever and include: a) What temperature should elicit an evaluation? b) When are blood cultures warranted? c) When should intravascular catheters be cultured or removed? d) When are cultures of respiratory secretions, urine, stool, or cerebral spinal fluid warranted? e) When are radiographic studies warranted? These practice parameters do not address children, since children have different issues that merit discussion in a separate document. In addition, these practice parameters do not address an approach to persistent fever after the initial evaluation, or to localized infection once the anatomic source of fever has been identified. These issues are addressed in other monographs or practice parameters. The current document also does not address the desirability or selection of empiric vs. specific therapy since the need for therapy is so dependent on clinical evaluation and the underlying disease. It did not appear to this task force that useful therapeutic guidelines could easily be provided which took into account the acuity of illness, the underlying disease process, concurrent drugs (i.e., immunosuppressive agents, and antimicrobials), ability to tolerate toxicities, and geographic antibiotic susceptibility differences. Each ICU must establish its own policies for evaluating fever that take into account the type of ICU involved (e.g., medical ICU, surgical ICU, burn ICU, etc.), the specific patient population (e.g., immunosuppressed vs. immunocompetent, elderly vs. younger adults), recent epidemics (e.g., out‐breaks of Clostridium difficile diarrhea or vancomycin‐resistant Enterococcus), or endemic pathogens (e.g., methicillin‐resistant Staphylococcus aureus). It is hoped that these practice parameters will assist intensivists and consultants as a starting point for developing an effective and cost conscious approach appropriate for their patient populations. The specific recommendations are rated by the strength of evidence, using the published criteria of the Society of Critical Care Medicine (Table 2). Table 2. Society of Critical Care Medicines rating system for strength of recommendation and quality of evidence supporting the references

Comparative In Vitro Activity and Clinical Pharmacology of Ticarcillin and Carbenicillin

The in vitro activity and human pharmacology of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared. There has been no increase in resistance to ticarcillin of Pseudomonas strains over the past 5 years, but resistance of indole-positive Proteus and Serratia strains has been documented. After intramuscular (i.m.) injection of 1 g of ticarcillin, mean peak levels occurred at 1 h (26.9 μg/ml) with a decline over 6 h (6.8 μg/ml). Serum half-life was 84 min. Dilution of ticarcillin lidocaine reduced pain on i.m. injection but did not alter serum levels. Blood levels after 1 g i.m. are adequate to treat infections produced by Escherichia coli, Proteus mirabilis, and some Enterobacter, but not Pseudomonas. After rapid intravenous infusion of 3 and 5 g, mean peak serum levels of ticarcillin were slightly lower for 1 h than those achieved with carbenicillin. Probenecid administered before infusion produced increases in blood levels, half-lives, and volume of distribution. The biological half-life of ticarcillin was 72 min compared to 66 min with carbenicillin. There was a larger volume of distribution for ticarcillin than carbenicillin (15 liters versus 14 liters). The ticarcillin half-life when administered with probenecid was 108 min. Urinary recovery of ticarcillin was 77% against 95% of carbenicillin. However, approximately 10% of ticarcillin is recovered as penicilloic acid so that 95% of an intravenously administered dose is recovered.

Sepsis and adrenal function

In the setting of sepsis, adrenal function can be difficult to evaluate. Cortisol levels, normally elevated by the stress of sepsis, are occasionally reduced, signifying possible adrenal dysfunction. Even elevated cortisol levels do not assure that adrenal reserve is adequate and may in fact portend a preterminal state. Bilateral adrenal hemorrhage leading to adrenal insufficiency is one complication of the sepsis syndrome. This endocrine rounds illustrates the importance in considering adrenal insufficiency and adrenal hemorrhage in patients with overwhelming sepsis while discussing the pathophysiology, clinical presentation, and therapeutic implications of this dire complication.

Sisomicin therapy of serious gram-negative infections

SummarySisomicin, a dehydrogenated gentamicin C1a derivative, was employed to treat serious gram-negative infections. A satisfactory clinical response was obtained in 79 % of 34 episodes of infection. Response was good even in the presence of preexisting renal or hepatic disease and in spite of concomitant use of immunosuppressive agents. Pseudomonas and Serratia urinary tract infections responded well with failure occurring only in patients with marked structural abnormalities. Pulmonary infections showed good clinical response in spite of failure to eliminate the organism from the sputum of patients with extensive underlying pulmonary disease. Although serious nephrotoxicity was not encountered, five patients had cylindruria or hematuria which was accompanied in two cases by a slight rise in serum creatinine. Furthermore, the precise meaning of cylindruria in acid urine is unclear. Transient vestibular abnormalities were seen in two of 34 episodes of treatment. Hematologic or hepatic abnormalities were not encountered.ZusammenfassungSisomicin, ein dehydriertes Gentamicin C1a-Derivat, wurde zur Behandlung schwerer gramnegativer Infektionen eingesetzt. Bei 79 % von 34 Infektionen wurden zufriedenstellende klinische Erfolge erzielt. Unter der Behandlung konnten sogar bei Fällen mit bereits bestehender Nieren- oder Lebererkrankung und trotz gleichzeitiger Gabe von Immunosuppressiva gute Erfolge verzeichnet werden. Harnwegsinfektionen, die durch Pseudomonas oder Serratia hervorgerufen wurden, sprachen ebenfalls gut an, außer bei Patienten mit deutlich ausgeprägten Anomalien. Bei Infektionen der Lunge waren die klinischen Ergebnisse gut, auch wenn bei ausgedehntem Grundleiden der Lunge die Keime nicht aus dem Sputum eliminiert werden konnten. Obwohl keine ernsthafte Nephrotoxizität auftrat, zeigen fünf Patienten Zylindrurie oder Hämaturie, die in zwei Fällen mit einem leichten Anstieg des Serumkreatinin einherging. Allerdings ist die genaue Bedeutung der Zylindrurie im sauren Harn noch unklar. Vorübergehende vestibuläre Störungen wurden bei zwei von 34 Behandlungen beobachtet. Es traten keine Blutbildungs- oder Leberstörungen auf.

Pharmacokinetics of sisomicin in normal patients and those with depressed renal function

SummaryThe pharmacokinetics of sisomicin were studied in 29 patients and seven patients on chronic hemodialysis. The mean peak serum levels after intramuscular injection were 3.55 µg/ml at 0.5 hours. Levels of 1.5 µg/ml were present at six hours. The mean half-life of the drug varied with the renal function. In normal individuals the half-life is 1.85 hours. The apparent volume of distribution is 17.9 liters. 81% of a dose is recovered in the urine in a 12 hour period. Sisomicin is removed by hemodialysis with an average half-life of six hours and 39% removed during a six-hour dialysis period.ZusammenfassungDie Pharmakokinetik des Sisomicin wurde bei 29 Patienten und bei sieben Patienten mit chronischer Haemodialyse untersucht. Die mittleren Serumspitzenspiegel nach intramuskulärer Injektion betrugen 3,55 µg/ml nach 1/2 Std. Sechs Std. nach der Injektion waren noch 1,5 µg/ml vorhanden. Die mittlere Halbwertszeit des Antibiotikums war von der Nierenfunktion abhängig. Bei normaler Nierenfunktion beträgt die Halbwertszeit 1,85 Std. und das Verteilungsvolumen 17,9 Liter. 81 % der verabreichten Dosis werden während 12 Std. im Harn wiedergefunden. Durch die Haemodialyse wird Sisomicin mit einer durchschnittlichen Halbwertszeit von 6 Std. eliminiert und 39 % wurden während einer 6stündigen Dialyse ausgeschieden.