Bayesian methods: a potential path forward for sepsis trials.

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

Increased Endotoxin Activity in COVID-19 Patients Admitted to the Intensive Care Unit.

OBJECTIVE: Endotoxin is a component of Gram-negative bacteria and can be measured in blood using the endotoxin activity assay (EAA). Endotoxin exposure initiates an inflammatory cascade that may contribute to organ dysfunction. Endotoxemia has been reported in previous viral pandemics and we investigated the extent of endotoxemia and its relationship to outcomes in critically ill patients with COVID-19. MATERIALS AND METHODS: We conducted a Prospective Cohort Study of 96 critically-ill COVID-19 patients admitted to the George Washington University Hospital ICU from 25 Mar-6 Jun 2020. EAA and inflammatory markers (ferritin, d dimer, IL-6, CRP) were measured on ICU admission and at the discretion of the clinical team. Clinical outcomes (mortality, LOS, need for renal replacement therapy (RRT), intubation) were measured. Statistical analysis was conducted using descriptive statistics and effect estimates with 95% confidence intervals. Comparisons were made using chi-square tests for categorical variables, and T-tests for continuous variables. RESULTS: A majority of patients (68.8%) had high EAA [≥ 0.60], levels seen in septic shock. Only 3 patients had positive bacterial cultures. EAA levels did not correlate with mortality, higher levels were associated with greater organ failure (cardiovascular, renal) and longer ICU LOS. Among 14 patients receiving RRT for severe AKI, one had EAA < 0.6 (p = 0.043). EAA levels did not directly correlate with other inflammatory markers. CONCLUSIONS: High levels of endotoxin activity were found in a majority of critically-ill COVID-19 patients admitted to the ICU and were associated with greater risk for cardiovascular and renal failure. Further investigation is needed to determine if endotoxin reducing strategies are useful in treating severe COVID-19 infection.

The Growth of Palliative Practice and End of Life Care in an Academic Teaching Intensive Care Unit.

OBJECTIVE: Dying in the intensive care unit (ICU) has changed over the last twenty years due to increased utilization of palliative care. We sought to examine how palliative medicine (PM) integration into critical care medicine has changed outcomes in end of life including the utilization of do not resuscitate (no cardiopulmonary resuscitation but continue treatment) and comfort care orders (No resuscitation, only comfort medication). Design: Retrospective observational review of critical care patients who died during admission between two decades, 2008 to 09 and 2018 to 19. Setting: Single urban tertiary care academic medical center in Washington, D.C. Patients: Adult patients who were treated in any ICU during the admission which they died. INTERVENTIONS AND MEASUREMENTS: We sought to measure PM involvement across the two decades and its association with end of life care including do not resuscitate (DNR) and comfort care (CC) orders. Main Results: 571 cases were analyzed. Mean age was 65 ± 15, 46% were female. In univariate analysis significantly more patients received PM in 2018 to 19 (40% vs. 27%, p = .002). DNR status increased significantly over time (74% to 84%, p = .002) and was significantly more common in patients who were receiving PM (96% vs. 72%, p < 0.001). CC also increased over time (56% to 70%, p = <0.001), and was more common in PM patients (87% vs. 53%, p < 0.001). Death in the ICU decreased significantly over time (94% to 86%, p = .002) and was significantly lower in PM patients (76% vs. 96%, p < 0.001). The adjusted odds of getting CC for those receiving versus those not receiving PM were 14.51 (5.49-38.36, p < 0.001) in 2008 to 09 versus 3.89 (2.27-6.68, p < 0.001) in 2018 to 19. Conclusion: PM involvement increased significantly across a decade in our ICU and was significantly associated with incidence of DNR and CC orders as well as the decreased incidence of dying in the ICU. The increase in DNR and CC orders independent of PM over the past decade reflect intensivists delivering PM services.

Characterization of end-of-life electroencephalographic surges in critically ill patients.

Neuromonitoring devices to assess level of sedation are now used commonly in many hospital settings. The authors previously reported that electroencephalicgraphic (EEG) spikes frequently occurred after the time of death in patients being neuromonitored at the time of cessation of circulation. In addition to the initial report, end-of-life electrical surges (ELES) have been subsequently documented in animal and human studies by other investigators. The frequency, character, intensity, and significance of ELES are unknown. Some have proposed that patients should not be declared dead for purposes of organ donation prior to the occurrence of an ELES. If clinical practice were altered to await the presence of an ELES, there could be detrimental consequences to donated organs and their recipients. To better characterize ELES, the authors retrospectively assessed the frequency and nature of ELES in serial patients. To better document ELES, they collected neuromonitoring, demographic, and clinical data on consecutive patients who expired while being actively monitored as part of their standard palliative care. These data were retrospectively collected when available as a convenience sample. The authors assessed 35 patients of which 7 were clinically confirmed as brain dead. None of the brain-dead patients displayed an ELES. Thirteen of the 28 remaining patients (46.4%) exhibited an ELES. The ELES observed were demonstrated to have high frequency EEG signal. The mean peak amplitude of ELES as measured by Patient State IndexTM (PSI) was 58.5 ± 25.7. In this preliminary assessment, the authors found that ELES are common in critically ill patients who succumb. The exact cause and significance of ELES remain unknown; further study is warranted.

Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity.

Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)±SEM of 0.87±0.09 (P<0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P<0.05). FST urine output was the only biomarker to significantly predict RRT (0.86±0.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (ΔAUC, P>0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed.

Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study.

INTRODUCTION: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown. METHODS: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg. RESULTS: ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00). CONCLUSION: Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min. TRIAL REGISTRATION: Clinicaltrials.gov NCT01393782. Registered 12 July 2011.

Safety and dose-finding study of activated protein C (drotrecogin alfa activated) as an anticoagulant in end-stage renal disease patients treated with hemodialysis.

BACKGROUND/AIMS: End-stage renal disease (ESRD) patients treated with hemodialysis (HD) experience a high risk of death. ESRD patients with elevated levels of pro-inflammatory cytokines are at increased risk of death from cardiovascular events and infection. HD is often facilitated by the use of an anticoagulant. We hypothesized that the use of an anticoagulant that also possessed anti-inflammatory qualities without significant immunosuppressive effects may reduce the risk of death. In this pilot study, we sought to determine the optimal dose of activated protein C (APC) to achieve adequate regional anticoagulation for HD and determine if the drug can be safely used in ESRD patients treated with HD. METHODS: Twelve stable HD patients were enrolled into this safety and dose-finding study. Varying doses of APC were administered in place of usual heparin at varying doses to determine the range of APC that can be used for extracorporeal circuit anticoagulation. Partial thromboplastin time was assessed at fixed intervals during the HD treatment. RESULTS: The average age of study patients was 49 ± 12 years. 75% of patients were African-American and 66.7% were male. The optimal dose of APC to induce adequate anticoagulation was 24-30 µg/kg/h. No patients experienced any serious adverse events. One patient had their infusion stopped early due to refractory intradialytic hypertension. CONCLUSIONS: For ESRD patients undergoing HD, an initial starting dose of 24-30 µg/kg/h achieves a target partial thromboplastin time that should be adequate for circuit anticoagulation. This dose appears safe and was well tolerated.

Development and standardization of a furosemide stress test to predict the severity of acute kidney injury.

INTRODUCTION: In the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages. METHODS: We investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of AKIN Stage-III in 2 cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients as part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critically ill patients who received their FST in the setting of early AKI. RESULTS: We studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p<0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%. CONCLUSIONS: The FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted.

Off-pump versus on-pump coronary artery bypass grafting outcomes stratified by preoperative renal function.

Clinical trials of off-pump coronary artery bypass grafting (CABG) have largely excluded patients with CKD. Here, we sought to determine whether pump status affects outcomes in patients with CKD. Using a nonrandomized cohort of 742,909 non-emergent, isolated CABG cases, which included 158,561 off-pump cases, in the Society of Thoracic Surgery Database from 2004 through 2009, we evaluated the association between pump status (off-pump versus on-pump) and in-hospital death or incident renal replacement therapy (RRT) across strata of preoperative renal function. We used propensity methods to adjust patient- and center-level analyses for imbalances in baseline patient risk. Patients who received on-pump and off-pump CABG had similar mean age and distribution of preoperative estimated GFR (eGFR). In a propensity-weighted analysis, off-pump CABG was associated with a reduction in the composite in-hospital death or RRT, with patients having lower preoperative renal function exhibiting greater benefit, on average. The risk difference (on-pump minus off-pump) ranged from 0.05 (95% confidence interval, -0.06 to 0.16) per 100 patients for eGFR ≥ 90 ml/min per 1.73 m(2) to 3.66 (95% confidence interval, 2.14-5.18) per 100 patients for eGFR 15-29 ml/min per 1.73 m(2). Both component endpoints suggested the same trend. In summary, these data suggest that patients with CKD experience less death or incident RRT when treated with off-pump compared with on-pump CABG. The reduction in incident RRT, not death, drove this effect on the composite among patients with low eGFR. Prospective trials comparing these procedures in patients with impaired preoperative renal function are warranted.

Treatment of addison disease and subsequent hypophosphatemic respiratory failure.

A 38-year-old man was found unresponsive with hypoglycemia by emergency medical service (EMS) personnel. He was intubated in the emergency department after reports of seizure activity. With supportive care and empiric steroids, the patient was extubated the next day. He reported a diagnosis of Addison disease and noncompliance with his steroid replacement therapy. Within 12 hours, respiratory failure and altered mental status required reintubation. Laboratory studies revealed rhabdomyolysis and hypophosphatemia. The replacement of glucose likely stimulated glycolysis, formation of phosphorylated glucose compounds, and an intracellular shift of phosphorus. This patient required phosphate replacement and was extubated on hospital day 5. We report a unique case of hypoglycemia due to Addison disease, leading to hypophosphatemic respiratory failure.

A residency style transition to practice program in trauma and critical care: The George Washington University Hospital experience.

ABSTRACT: Transition to practice programs for nurse practitioners and physician assistants are gaining popularity and becoming more specialized. As these providers seek opportunities to strengthen their clinical skills and bridge the gap from school to practice, it is important to recognize the benefits and barriers of such programs. In this article, The George Washington University Hospital shares its experience in managing a transition to practice program for trauma and critical care.

Utilization of base deficit and reliability of base deficit as a surrogate for serum lactate in the peri-operative setting.

BACKGROUND: Base deficit (BD) is commonly used in the operating room (OR) as an endpoint of resuscitation. BD is used as a surrogate marker for the accumulation of lactic acid(Lac). However, the BD can be affected by large amounts of saline. METHODS: We conducted a survey of anesthesiologists regarding the use of BD. We also studied the reliability of BD to determine the presence of hyperlactatemia (HL). Patients undergoing general anesthesia were eligible for enrollment if they were receiving an arterial line as part of their routine care. If an arterial blood gas was drawn by the operative team as part of the routine care, the remainder of the unused blood was also used to measure Lac. SURVEY: 73 staff anesthesiologists were surveyed. Over 70% of respondents used BD as an endpoint of resuscitation.Base Deficit Study: 35 patients were enrolled resulting in 88 arterial blood gases with corresponding Lac. Mean age was 61.4 ± 14.3 years, 43% were male. Mean pH was 7.39 ± 0.05, the mean bicarbonate was 23.0 ± 2.3 meq/L, the mean BD 1.34 ± 2.3, and the mean Lac was 1.58 ± 0.71 mmol/L. Mean ASA risk score was 3.16 ± 0.71. ROC area under the curve for base deficit to detect HL was 0.58. CONCLUSION: BD can often mislead the clinician as to the actual Lac. Lac can now be measured in the OR in real time. Therefore, if clinicians in the operative setting want to know the Lac, it should be measured directly.

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia.

BACKGROUND: Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. METHODS: We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L. RESULTS: From 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 +/- 15.7 years. Mean Lac was 2.11 +/- 2.6 mmol/L, mean AG was 9.0 +/- 5.1, mean ACAG was 14.1 +/- 3.8, mean BD was 1.50 +/- 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively. CONCLUSION: AG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.

Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes.

BACKGROUND: The diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Circulating blood cells may carry informative changes in their RNA expression profile that would signal internal infection or inflammation of the appendix. METHODS: Genome-wide expression profiling was applied to whole blood RNA of acute appendicitis patients versus patients with other abdominal disorders, in order to identify biomarkers of appendicitis. From a large cohort of emergency patients, a discovery set of patients with surgically confirmed appendicitis, or abdominal pain from other causes, was identified. RNA from whole blood was profiled by microarrays, and RNA levels were filtered by a combined fold-change (>2) and p value (<0.05). A separate set of patients, including patients with respiratory infections, was used to validate a partial least squares discriminant (PLSD) prediction model. RESULTS: Transcript profiling identified 37 differentially expressed genes (DEG) in appendicitis versus abdominal pain patients. The DEG list contained 3 major ontologies: infection-related, inflammation-related, and ribosomal processing. Appendicitis patients had lower level of neutrophil defensin mRNA (DEFA1,3), but higher levels of alkaline phosphatase (ALPL) and interleukin-8 receptor-ß (CXCR2/IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR). CONCLUSIONS: Patients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil innate defense systems. The low defensin mRNA levels suggest that appendicitis patient's immune cells are not directly activated by pathogens, but are primed by diffusible factors in the microenvironment of the infection. The detected biomarkers are consistent with prior evidence that biofilm-forming bacteria in the appendix may be an important factor in appendicitis.

Modification of continuous venovenous hemodiafiltration with single-pass albumin dialysate allows for removal of serum bilirubin.

A 53-year-old woman was admitted to the hospital with ischemic colitis and underwent a subtotal colectomy. She developed acute renal failure, severe hyperbilirubinemia, and intense pruritus resistant to medical treatment. Extracorporeal albumin dialysis using a Molecular Adsorbent Recirculating System (MARS; Gambro Co, Lund, Sweden) has been used to treat liver failure and reduce total serum bilirubin (SB) levels. A trial of extracorporeal albumin dialysis with continuous renal replacement therapy (RRT) was instituted to achieve net removal of SB. A 25% albumin solution was mixed with conventional dialysate to yield a dialysate concentration of 1.85% or 5.0% albumin. The patient underwent 2 continuous RRT sessions using extracorporeal albumin dialysis (1.85% and 5.0% albumin dialysate). Pretreatment and posttreatment SB levels were determined, and total bilirubin concentration (TB) also was measured in each of the collection bags during conventional and albumin dialysis. Pretreatment and posttreatment SB levels were 50.4 mg/dL (862 micromol/L) and 39.0 mg/dL (667 micromol/L) with 1.85% albumin dialysate and 47.1 mg/dL (805 micromol/L) and 39.7 mg/dL (679 micromol/L) with 5.0% albumin dialysate, respectively. The collected dialysate TB level was 0.3 mg/dL (5 micromol/L) during nonalbumin RRT and increased to 1.37 +/- 0.06 mg/dL (23 +/- 1 micromol/L) with 1.85% albumin dialysis. The collected dialysate fluid TB level was 0.3 mg/dL (5 micromol/L) during the nonalbumin RRT and increased to 1.38 +/- 0.15 mg/dL (24 +/- 3 micromol/L) during 5.0% albumin RRT. Single-pass albumin dialysis with continuous RRT cleared SB better than standard continuous RRT. Single-pass albumin dialysis with continuous RRT is feasible and may be a viable alternative in centers that do not have access to MARS therapy. This modality merits additional evaluation for its efficacy in clearing albumin-bound serum toxins.

Lactate concentration gradient from right atrium to pulmonary artery.

INTRODUCTION: We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA. METHODS: A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, O2 saturation (SO2) and [Lac]. We defined Delta[Lac] as ([Lac]ra - [Lac]pa), DeltaSO2 as (SraO2 - SpaO2) and the change in O2 consumption (DeltaVO2) as the difference in systemic VO2 calculated using Fick's equation with either SraO2 or SpaO2 in place of mixed venous SO2. Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman. RESULTS: We found SraO2 > SpaO2 (74.2 +/- 9.1 versus 69.0 +/- 10.4%; p < 0.001) and [Lac]ra > [Lac]pa (3.9 +/- 3.0 versus 3.7 +/- 3.0 mmol x l-1; p < 0.001). Delta[Lac] correlated with DeltaVO2 (r2 = 0.34; p < 0.001). CONCLUSION: We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO2 and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO2 and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Delta[Lac].

Lack of equivalence between central and mixed venous oxygen saturation.

STUDY OBJECTIVE: We compared paired samples of central venous O(2) saturation (Scvo(2)) and mixed venous O(2) saturation (Svo(2)) to test the hypothesis that Scvo(2) is equivalent to Svo(2). We also compared O(2) consumption (Vo(2)) computed with Scvo(2) (Vo(2)cv) to that computed with Svo(2) (Vo(2)v). DESIGN: Prospective, sequential, observational study. SETTING: Combined medical-surgical ICU. PATIENTS: Fifty-three individuals > 18 years of age of either sex who required a pulmonary artery catheter (PAC) to guide fluid therapy. Subjects were identified as postsurgical (32 patients) or medical (21 patients) according to their ICU admission diagnosis. INTERVENTIONS: A PAC was inserted through the internal jugular or subclavian veins. Care was taken to place the PAC proximal port approximately 3 cm above the tricuspid valve. Blood samples were drawn from the proximal and distal ports in random order. An arterial blood sample also was drawn. MEASUREMENTS: Cardiac output in triplicate, systemic pressure, and central pressure. We analyzed blood samples for hemoglobin concentration and O(2) saturation (So(2)). Data were compared by correlation analysis and by the method of Bland and Altman. RESULTS: Svo(2) was consistently lower than Scvo(2) (p < 0.0001), with a mean (+/-SD) bias of -5.2 +/- 5.1%. Similar differences in Scvo(2) and Svo(2) were present within each subgroup (p < 0.001). A lower Svo(2) resulted in Vo(2)v values that were higher than the Vo(2)cv values for all patients in the study (mean Vo(2)v, 236.7 +/- 103.4 mL/min; mean Vo(2)cv, 191.1 +/- 84.0 mL/min; p < 0.001) as well as for patients within each subgroup (p < 0.001). CONCLUSIONS: Measurements of Scvo(2) and Svo(2) were not equivalent in this sample of critically ill patients. Moreover, substituting Scvo(2) for Svo(2) in the calculation of Vo(2) produced unacceptably large errors. The decrease in So(2) between Scvo(2) to Svo(2) may result from the mixing of atrial and coronary sinus blood. As such, this difference may be a marker of myocardial O(2) consumption.