Does intraoperative blood loss affect antibiotic serum and tissue concentrations?

OBJECTIVE: To determine the effect of intraoperative blood loss on prophylactic cefazolin and gentamicin serum and tissue concentrations. DESIGN: A prospective study of elective spinal instrumentation surgical procedures with an expected large blood loss. SETTING: Tertiary care, inner-city university hospital. PATIENTS: Eleven adult patients who underwent an elective surgical procedure that involved spinal instrumentation. INTERVENTION: Standard perioperative administration of a combination of cefazolin and gentamicin. Serum and tissue samples were obtained consecutively throughout the surgical procedure. MAIN OUTCOME MEASURES: The effect of intraoperative blood loss on serum and tissue cefazolin and gentamicin concentrations and their pharmacokinetics. RESULTS: At the time of the incision, serum cefazolin concentrations were greater than tissue concentrations (P = .07). A mean dose of 1.8-mg/kg gentamicin yielded low or nontherapeutic serum and tissue gentamicin concentrations. Cefazolin and gentamicin were eliminated from the tissue compartment slower than from the serum compartment (P < .03), while the half-life of cefazolin was significantly (P = .06) longer in the tissue compartment. The volume of distribution of cefazolin was normal (ie, 12.5 L), while the volume of distribution of gentamicin was 5-fold greater than expected. At 60 minutes after the incision, blood loss correlated with cefazolin tissue concentrations (r = -0.66, P = .05). Blood loss correlated with the change in tissue antibiotic concentrations for cefazolin (r = 0.73, P = .04). In addition, the clearance of gentamicin from the tissues correlated with blood loss (r = 0.82, P = .01). CONCLUSIONS: Based on measured pharmacokinetic values, additional doses of cefazolin should be administered when the operation exceeds 3 hours and blood loss is greater than 1500 mL. Doses of gentamicin greater than 1.8 mg/kg should be administered more than 30 minutes prior to the surgical incision.

Risk factors and clinical impact of central line infections in the surgical intensive care unit.

OBJECTIVE: To determine the risk factors and clinical impact of central line infections in critically ill surgical patients. DESIGN: Retrospective study. SETTING: The surgical intensive care unit of a large tertiary care university hospital. PATIENTS: A total of 232 consecutive central line catheters sent for culture from patients in a surgical intensive care unit during 1996 and 1997. Catheters were sent for microbiologic analysis when the patient was clinically infected and the central line was a possible source. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Risk factors associated and clinical impact of a positive catheter culture. RESULTS: Of 232 consecutive catheters from 93 patients sent for microbiologic analysis, 114 catheters (49%) had no growth, 40 (17%) were colonized (<15 colonies), and 78 (34%) were considered infected (> or =15 colonies). Univariate analysis showed that site (internal jugular vs subclavian, P<.001), catheter use (monitoring > dialysis > fluid > nutrition, P=.006), placement in the operating room vs the intensive care unit (P=.02), and placement of a new catheter (> guide wire, > new site, P=.003) were all significant factors. Surprisingly, neither the number of lunmens nor the duration of the catheter in situ were predictors when a catheter was suspected and not proved infected compared with a suspected and proved catheter infection. In the multiple regression model, the placement of the catheter in the internal jugular position was the single most important predictor of a catheter infection (P<.001; odds ratio, 1.83; 95% confidence interval [CI], 1.41-2.37). The presence or absence of a specific clinical sign of infection was not predictive of a proved catheter infection. Eighty-six percent of patients had gram-positive bacteria identified on the culture, while the remaining patients had gram-negative bacteria or Candida identified. Of the catheter infections, 68% were monomicrobial, whereas 32% were polymicrobial. Of the catheters sent for microbiologic analysis, 209 (90%) had concurrent peripheral blood cultures for analysis. Nineteen (32%) with no growth from the catheter, and 14 (23%) of colonized catheters had concurrent bacteremia; all had another identifiable cause of infection. Twenty-seven (45%) of infected catheters had a concurrent bacteremia, and 9 of 27 had a second site positive for the same organism. Death related to the infection occurred in 15 patients, 2 in the first 72 hours and 13 in the following 14 days. CONCLUSIONS: Central line infections remain an important cause of morbidity and mortality. Comprehensive review of hospital practices may show a directed focus for performance improvement practices. At our institution, internal jugular catheters have the highest rate of infection. This may suggest breaks in technique during catheter insertion or during catheter maintenance and care.

Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit.

HYPOTHESIS: Catheter-related bloodstream infection (CRBSI) in critically ill surgical patients with prolonged intensive care unit (ICU) stays is associated with a significant increase in health care resource use. DESIGN: Prospective cohort study. SETTING: Surgical ICU at a large tertiary care center. PATIENTS: Critically ill surgical patients (N = 260) with projected surgical ICU length of stay greater than 3 days. INTERVENTIONS: Central venous catheters were cultured for clinical suspicion of infection. MAIN OUTCOME MEASURES: Increases in total hospital cost, ICU cost, hospital days, and ICU days attributable to CRBSI were estimated using multiple linear regression after adjusting for demographic factors and severity of illness (APACHE III [Apache Physiology and Chronic Health Evaluation III] score). RESULTS: The incidence of CRBSI per 1000 catheter-days was 3.6 episodes (95% confidence interval [CI], 2.1-5.8 episodes). Microbiologic isolates were Gram-positive bacteria in 75%, Gram-negative bacteria in 20%, and yeast in 5%. After adjusting for demographic factors and severity of disease, CRBSI was associated with an increase of $56 167 (95% CI, $11 523-$165 735; P =.001) (in 1998 dollars) in total hospital cost, an increase of $71 443 (95% CI, $11 960-$195 628; P<.001) in ICU cost, a 22-day increase in hospital length of stay, and a 20-day increase in ICU length of stay. CONCLUSIONS: For critically ill surgical patients, CRBSI is associated with a profound increase in resource use. Prevention, early diagnosis, and intervention for CRBSI might result in cost savings in this high-risk population.

Handwashing compliance depends on professional status.

BACKGROUND: Nosocomial infections can be transmitted from microorganisms on the hands of health care workers to patients. Handwashing (HW) has a proven benefit in preventing transmission of infection, yet compliance with handwashing, especially in intensive care units, ranges between 28% and 74%. METHODS: To determine if HW behavior varies as a function of health care professional status and patient interaction, we conducted an observational study of a surgical intermediate care unit in a large university teaching hospital. HW compliance was observed among all health care workers (HCW): physicians (MD; N = 46), nurses (RN; N = 295), and nursing support personnel (NSP; N = 93). Over an 8-week period, unidentified, trained observers documented all HCW interactions in 1-h random blocks. HW opportunities were classified into low and high risk of pathogen acquisition and transmission. RESULTS: A total of 493 HW opportunities were observed, of which 434 involved MD, RN, and NSP. Two hundred and sixty-one low-risk (MD 35, RN 171, NSP 55) and 173 (MD 11, RN 124, NSP 38) high-risk interactions were observed. Overall HW rates were low (44%). Significant differences existed among HCW, with MDs being the least likely to wash (15% versus RN 50%, NSP 37%, p < 0.01). In adjusting for high-risk situations, MDs (odds ratio [OR] 5.58, 95% CI 2.49-12.54; NSP, OR 1.73, 95% CI 1.13-2.64; RN, OR 0.98, 95% CI 0.77-1.23) were significantly less likely to perform HW when compared to RNs. Nursing groups were significantly less likely to wash in low-risk versus high-risk situations (MD 9.2% versus 17.1%; RN 69.4% versus 39.6%; NSP 85% versus 23.3%), suggesting individual discrimination of the importance of HW. Although nurses were less likely to wash in high-risk situations compared to NSP, the overall number of opportunities was greater, suggesting that improvement in HW to the level of NSP could have a major impact on infection transmission. CONCLUSION: Significant opportunities exist for quality improvement, novel educational strategies, and assessment of reasons why MDs and, to a lesser extent, RNs fail to follow simple HW practices.

The diagnostic value of fungal surveillance cultures in critically ill patients.

BACKGROUND: Heavy fungal colonization is a known risk factor for fungal infection, yet the value of fungal surveillance cultures is uncertain. METHODS: To evaluate the utility of fungal surveillance cultures in predicting fungal infections, we evaluated surveillance fungal cultures over a three month period in a prospective, cohort study conducted at a university medical center with a large tertiary referral population. We enrolled 172 patients in the Oncology Center and the medical and surgical intensive care units at Johns Hopkins Hospital. RESULTS: Surveillance cultures from five sites were obtained twice weekly and evaluated for prediction of subsequent fungal infection. Infections were prospectively defined and evaluated by a panel of clinicians. Test characteristics were assessed. Of 159 eligible patients, 14 (9%) developed invasive fungal infections. Having two or more surveillance sites positive in a single day had an odds ratio of 8.2 (1.1-358.0) (p = 0.03), a negative predictive value of 0.98, sensitivity of 0.92, and a likelihood ratio of 1.6 for a fungal infection. In a multiple logistic regression model and Kaplan-Meier analysis, fungal burden was strongly and independently associated with infection (p < 0.05). CONCLUSIONS: Surveillance cultures are helpful in determining fungal colonization but do not have a high positive predictive value for fungal infection in a broad population of intensive care unit patients. However, fungal infection is more likely in heavily colonized patients, and surveillance cultures show that fungal infection is extremely unlikely in patients without fungal colonization.

Effect of nurse-to-patient ratio in the intensive care unit on pulmonary complications and resource use after hepatectomy.

BACKGROUND: Nurse-to-patient ratios in the intensive care unit are associated with postoperative mortality, morbidity, and costs after some high-risk surgery. OBJECTIVE: To determine if having 1 nurse caring for 1 or 2 patients ("more nurses") versus 1 nurse caring for 3 or more patients ("fewer nurses") in the intensive care unit at night is associated with differences in clinical and economic outcomes after hepatectomy. METHODS: Statewide observational cohort study of 569 adults who had hepatic resection, 1994 to 1998. Hospital discharge data were linked to a prospective survey of organizational characteristics in the intensive care unit. Multivariate analysis was used to determine the association of nighttime nurse-to-patient ratios with in-hospital mortality, length of stay, hospital costs, and specific postoperative complications. RESULTS: A total of 240 patients at 25 hospitals had fewer nurses; 316 patients in 8 hospitals had more nurses. No significant association between nighttime nurse-to-patient ratios and in-hospital mortality was detected. The overall complication rate was 28%. By univariate analysis, patients with fewer nurses had increased risks for pulmonary failure (5.8% vs 1.6%, relative risk, 3.6; 95% CI, 1.3-10.1; P=.006) and reintubation (10.8% vs 1.9%, relative risk, 5.7; 95% CI, 2.4-13.7; P<.001). By multivariate analysis, patients with fewer nurses had increased risk for reintubation (odds ratio, 2.9; 95% CI, 1.0-8.1; P=.04) and a 14% increase (95% CI, 3%-23%; P=.007) or an additional $1248 (95% CI, $384-$2112; P = .005) in total hospital costs. CONCLUSIONS: Fewer nurses at night is associated with increased risk for specific postoperative pulmonary complications and with increased resource use in patients undergoing hepatectomy.

Sickness Impact Profile Score versus a Modified Short-Form survey for functional outcome assessment: acceptability, reliability, and validity in critically ill patients with prolonged intensive care unit stays.

BACKGROUND: Quality of life after surgical critical illness is an important measure of outcome. The Sickness Impact Profile Score (SIP) has been validated in critically ill patients, but the Modified Short-Form (MSF) has not been directly compared with it. METHODS: The SIP and MSF-36 were coadministered to 127 patients (surrogates) with a prolonged surgical critical illness at baseline at 1, 3, 6, and 12 months. Reliability, validity, and acceptability were determined for overall and subscores at each time point. RESULTS: The overall SIP and eight subscores, including physical health and psychosocial health, were all significantly improved at 1 year compared with baseline (p < 0.05). However, the MSF-36 was improved only in health perception (p < 0.05), but pain scores were higher (p < 0.05) than at baseline. Internal consistency of the MSF-36 was poor at 1 and 3 months. Correlation between the tools was excellent at baseline and 1 year but variable in overall and subscores at other time points. CONCLUSION: The SIP is more comprehensive, reliable, and acceptable in determining specific quality-of-life abnormalities, but the MSF-36 is easier to administer and correlates well at baseline and 1 year in patients with a prolonged critical illness.

Survival and functional outcome after prolonged intensive care unit stay.

OBJECTIVE: To examine the functional outcome and costs of a prolonged illness requiring a stay in the surgical intensive care unit (SICU) of 7 of more days. SUMMARY BACKGROUND DATA: The long-term benefits and costs after a prolonged SICU stay have not been well studied. METHODS: All patients with an SICU length of stay of 7 or more days from July 1, 1996, to June 30, 1997, were enrolled. One hundred twenty-eight patients met the entry criteria, and mortality status was known in 127. Functional outcome was determined at baseline and at 1, 3, 6, and 12 months using the Sickness Impact Profile score, which ranges from 0 to 100, with a score of 30 being severely disabled. Hospital costs for the index admission and for all readmissions to Johns Hopkins Hospital were obtained. All data are reported as median values. RESULTS: For the index admission, age was 57 and APACHE II score was 23. The initial length of stay in the ICU was 11 days; the hospital length of stay was 31 days. The Sickness Impact Profile score was 20.2 at baseline, 42.9 at 1 month, 36.2 at 3 months, and 20.3 at 6 months, and was lower than baseline at 1 year. The actual 1-year survival rate was 45.3%. The index admission median cost was $85,806, with 65 total subsequent admissions to this facility. The cost for a single 1-year survivor was $282,618 (1996). CONCLUSIONS: An acute surgical illness that results in a prolonged SICU stay has a substantial in-hospital death rate and is costly, but the functional outcome from both a physical and physiologic standpoint is compatible with a good quality of life.

Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients.

OBJECTIVE: To evaluate the prophylactic use of enteral fluconazole to prevent invasive candidal infections in critically ill surgical patients. SUMMARY BACKGROUND DATA: Invasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant patients, few studies have focused on surgical patients and prevention of fungal infection. METHODS: The authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU). A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral fluconazole 400 mg or placebo per day during their stay in the surgical ICU at Johns Hopkins Hospital. RESULTS: The primary end point was the time to occurrence of fungal infection during the surgical ICU stay, with planned secondary analysis of patients "on-therapy" and alternate definitions of fungal infections. In a time-to-event analysis, the risk of candidal infection in patients receiving fluconazole was significantly less than the risk in patients receiving placebo. After adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed between patients receiving fluconazole and those receiving placebo. CONCLUSIONS: Enteral fluconazole safely and effectively decreased the incidence of fungal infections in high-risk, critically ill surgical patients.

Surveillance strategies and impact of vancomycin-resistant enterococcal colonization and infection in critically ill patients.

OBJECTIVE: To determine the optimal site and frequency for vancomycin-resistant enterococci (VRE) surveillance to minimize the number of days of VRE colonization before identification and subsequent isolation. SUMMARY BACKGROUND DATA: The increasing prevalence of VRE and the limited therapeutic options for its treatment demand early identification of colonization to prevent transmission. METHODS: The authors conducted a 3-month prospective observational study in medical and surgical intensive care unit (ICU) patients with a stay of 3 days or more. Oropharyngeal and rectal swabs, tracheal and gastric aspirates, and urine specimens were cultured for VRE on admission to the ICU and twice weekly until discharge. RESULTS: Of 117 evaluable patients, 23 (20%) were colonized by VRE. Twelve patients (10%) had VRE infection. Of nine patients who developed infections after ICU admission, eight were colonized before infection. The rectum was the first site of colonization in 92% of patients, and positive rectal cultures preceded 89% of infections acquired in the ICU. This was supported by strain delineations using pulsed-field gel electrophoresis. Twice-weekly rectal surveillance alone identified 93% of the maximal estimated VRE-related patient-days; weekly or admission-only surveillance was less effective. As a test for future VRE infection, rectal surveillance culture twice weekly had a negative predictive value of 99%, a positive predictive value of 44%, and a relative risk for infection of 34. CONCLUSIONS: Twice-weekly rectal VRE surveillance of critically ill patients is an effective strategy for early identification of colonized patients at increased risk for VRE transmission, infection, and death.