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.

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.

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.

Neurogenic pulmonary edema: successful treatment with IV phentolamine.

Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

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.

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.

Femoral-based central venous oxygen saturation is not a reliable substitute for subclavian/internal jugular-based central venous oxygen saturation in patients who are critically ill.

BACKGROUND: Central venous oxygen saturation (Scv(O(2))) has been used as a surrogate marker for mixed venous oxygen saturation (Sv(O(2))). Femoral venous oxygen saturation (Sfv(O(2))) is sometimes used as a substitute for Scv(O(2)). The purpose of this study is to test the hypothesis that these values can be used interchangeably in a population of patients who are critically ill. METHODS: We conducted a survey to assess the frequency of femoral line insertion during the initial treatment of patients who are critically ill. Scv(O(2)) vs Sfv(O(2)) STUDY: Patients with femoral and nonfemoral central venous catheters (CVCs) were included in this prospective study. Two sets of paired blood samples were drawn simultaneously from the femoral and nonfemoral CVCs. Blood samples were analyzed for oxygen saturation and lactate. RESULTS: One hundred and fifty physicians responded to the survey. More than one-third of the physicians insert a femoral line at least 10% of the time during the initial treatment of patients who were critically ill. Scv(O(2)) vs Sfv(O(2)) STUDY: Thirty-nine patients were enrolled. The mean Scv(O(2)) and Sfv(O(2)) were 73.1% +/- 11.6% and 69.1% +/- 12.9%, respectively (P = .002), with a mean bias of 4.0% +/- 11.2% (95% limits of agreement: -18.4% to 26.4%). The mean serum lactate from the nonfemoral and femoral CVCs was 2.84 +/- 4.0 and 2.72 +/- 3.2, respectively (P = .15). CONCLUSIONS: This study revealed a significant difference between paired samples of Scv(O(2)) and Sfv(O(2)). More than 50% of Scv(O(2)) and Sfv(O(2)) values diverged by > 5%. Sfv(O(2)) is not always a reliable substitute for Scv(O(2)) and should not routinely be used in protocols to help guide resuscitation.

Surges of electroencephalogram activity at the time of death: a case series.

Abstract Level of consciousness at the end of life in critically ill patients is poorly characterized. We report a case series of seven patients who were neurologically intact before the decision to withdraw care due to extensive systemic critical illness. As part of our end-of-life care protocol, bispectral index (BIS) monitor (Aspect Medical Systems, Newton, MA) or SEDline (Hospira, Lake Forest, IL) monitoring devices are placed on each patient to ensure adequate comfort. Both monitoring systems use an integer-based system (BIS or PSI, respectively) to reflect the level of consciousness/effect of anesthesia. In each case, loss of blood pressure, as monitored by indwelling arterial line, was followed by a decline is BIS/PSI activity followed by a transient spike in BIS/PSI activity that approached levels normally associated with consciousness. This spike in electroencephalogram (EEG) activity had short duration and the activity then declined to a level of activity associated with burst suppression. In one case of a patient who had a SEDLine device, we were able to capture and analyze the raw EEG signal, and confirm that the EEG waveform was not artifact, and in fact a high frequency waveform was present during the spike activity. We speculate that this level of BIS/SEDline activity is related to the cellular loss of membrane polarization due to hypoxemia. We further speculate that since this increase in electrical activity occurred when there was no discernable blood pressure, patients who suffer "near death" experiences may be recalling the aggregate memory of the synaptic activity associated with this terminal but potentially reversible hypoxemia.

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.

Anion gap, anion gap corrected for albumin, and base deficit fail to accurately diagnose clinically significant hyperlactatemia in critically ill patients.

Anion gap, anion gap corrected for serum albumin, and base deficit are often used as surrogates for measuring serum lactate. None of these surrogates is postulated to predict hyperlactatemia in the critically ill. We prospectively collected data from September 2004 through August 2005 for 1381 consecutive admissions. Patients with renal disease, ketoacidosis, or toxic ingestion were excluded. Anion gap, anion gap corrected for albumin, and base deficit were calculated for all patients. We identified 286 patients who met our inclusion or exclusion criteria. The receiver-operating characteristic area under the curve for the prediction of hyperlactatemia for anion gap, anion gap corrected for albumin, and base deficit were 0.55, 0.57, and 0.64, respectively. Anion gap, anion gap corrected for albumin, and base deficit do not predict the presence or absence of clinically significant hyperlactatemia. Serum lactate should be measured in all critically ill adults in whom hypoperfusion is suspected.

Elevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsis.

Acute kidney injury (AKI) is common in critically ill patients with severe sepsis (SS), and the predictors of AKI in this population have not been well characterized. The study group was the placebo group of the Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) data set. PROWESS is a prospective, randomized, controlled study of the use of drotrecogin alpha (activated) for the treatment of SS. Placebo patients who had an admission renal sepsis organ failure score of 2 or more were excluded. AKI was defined as an increase in serum creatinine of 25% or 0.3 mg/dl during the first week postbaseline. The incidence of relevant parameters was then compared in patients with and without AKI. Half of the patients were randomly assigned to a model-building data set, and multivariable Cox regression was used to determine risk factors. Factors that remained significant in the remaining "model validation" data set were considered significant. Of the 840 patients in the placebo group, 547 met inclusion criteria. Of the 547 patients, 127 (23.2%) patients met criteria for AKI. The mean age of the 547 patients was 59.8 +/- 17.0, and 43.3% of the cohort were female. The ethnicity breakdown was as follows: White 83.2%, black 5.9%, and other 11%. Univariate analyses indicated that patients with AKI had a higher incidence of a dependence on the basis of activity of daily living scale (38.6 versus 26.7%; P = 0.01), a lower baseline platelet count (193,000 versus 222,000; P = 0.02), a higher baseline respiratory Sepsis Organ Failure Assessment score (2.9 versus 2.7; P = 0.02), higher preinfusion Acute Physiology and Chronic Health Evaluation II (APACHE II) score (24.8 versus 22.0; P = 0.0002), older age (63.7 versus 58.7 yr; P = 0.008), and higher log IL-6 (6.6 versus 5.8; P = 0.0006). In a multivariable Cox regression, the predictors of AKI were log IL-6 (P < 0.0001) and APACHE II (P = 0.0008). Increased log IL-6 and APACHE II score are significant risk factors of AKI in patients with SS. IL-6 data and the absence of correlation with measures of hypotension (e.g., mean arterial pressure, dosage of vasopressors) support the notion that inflammation is a significant component of AKI in SS.

Identifying critically ill patients at high risk for developing acute renal failure: a pilot study.

BACKGROUND: Acute renal failure (ARF) occurs commonly in the intensive care unit (ICU), but predicting which patients will develop ARF is difficult. We set out to determine which risk factors would predict the development of ARF in critically ill patients who are admitted to the ICU without ARF. METHODS: From August 2002 to April 2003, we enrolled medical-surgical ICU admissions into a cohort using a sampling tool based on their risk factor (RF) profile. The risk factors we identified were separated into 3 categories: chronic major, chronic minor, and acute RFs. Combinations of these RFs were used to create a sampling tool and identify patients to enroll into our cohort. Patients with end-stage renal disease and ARF upon admission to the ICU were excluded. RESULTS: We enrolled 194 patients over a 14-month period. The mean age of the cohort was 64.6 +/- 14.7 years. The percentage of Caucasians, African Americans, and Hispanics was 40.7%, 50.5%, and 3.6%, respectively. In a univariate analysis of the entire cohort, increasing APACHE II quartile, increased A-a gradient, presence of systemic inflammatory response syndrome (SIRS), decreased levels of serum albumin, and presence of active cancer predicted ARF. In a multiple logistic regression analysis, decreased serum albumin (high levels of serum albumin were protective), increased A-a gradient, and cancer were associated with development of ARF (OR 2.17, 1.04, and 2.86, respectively). CONCLUSION: Decreased levels of serum albumin concentration, increased A-a gradient, and presence of active cancer predict which patients who are admitted to the ICU will develop ARF.

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].