Comparison of cellulose diacetate and polysulfone membranes in the outcome of acute renal failure. A prospective randomized study.

BACKGROUND: Whether the nature of haemodialysis (HD) membranes can influence the outcome of acute renal failure (ARF) remains debatable. Recent studies have suggested that dialysis with bioincompatible unsubstituted cellulosic membranes is associated with a less favourable patient outcome than dialysis with biocompatible synthetic membranes. Since we generally use a modified cellulosic membrane with substantially lower complement- and leukocyte-activating potential than cuprophane, for dialysis of patients with ARF, and because there are no data in the literature regarding the influence of modified cellulosic membranes on the outcome of patients with ARF, we compared the outcome of ARF patients dialysed either with cellulose diacetate or with a synthetic polysulfone membrane. We also investigated the potential role of permeability by comparing membranes with high-flux versus low-flux characteristics. METHODS: This prospective, randomized, single centre study included 159 patients with ARF requiring HD. Patients were stratified according to age, gender, and APACHE II score and then randomized in chronological order to one of three dialysis membranes: low-flux polysulfone, high-flux polysulfone and meltspun cellulose diacetate. RESULTS: Aetiologies of ARF and the prevalence of oliguria were similarly distributed among the three groups. There was no significant difference between the three groups for survival (multivariate Cox's proportional hazards model, P=0.57), time necessary to recover renal function (P=0.82), and number of dialysis sessions required before recovery (P=0.86). Multivariate analysis showed that survival was significantly influenced only by the severity of the disease state (APACHE III score, P<0.0001), but not by the nature of the dialysis membrane (P=0.57) or the presence of oliguria (P=0.24). CONCLUSIONS: Among patients with ARF requiring HD survival and recovery time are not significantly influenced by the use of either meltspun cellulose diacetate or the more biocompatible high-flux or low-flux polysulfone. Dialysis using modified cellulose membranes is just as effective as dialysis using synthetic polysulfone membranes, but at a lower cost. In addition, the flux of the membrane did not influence patient outcome.

[Does the biocompatibility of the hemodialysis membrane influence the prognosis of acute renal insufficiency?]. / La biocompatibilité de la membrane d'hémodialyse influence-t-elle le pronostic de l'insuffisance rénale aiguë?

Several recent publications have suggested that the use of cuprophane in the setting of acute renal failure is associated with a higher mortality (especially from sepsis) and a slower recovery of renal function in the survivors in comparison with more biocompatible membranes. We present here a critical review of these publications and point to several methodological bias that might invalidate their conclusions. However, while waiting further information, we would advocate to abandon the use of cuprophane to dialyze patients with acute renal failure.

Effects of positioning and exercise on intracranial pressure in a neurosurgical intensive care unit.

BACKGROUND AND PURPOSE: The purpose of the study was to assess the safety of physical therapy by investigating its effects on intracranial pressure (ICP) and cerebral perfusion pressure. SUBJECTS: The subjects were 65 patients in a neurosurgical intensive care unit who had normal ICP (< 15 mm Hg) or increased ICP (> 15 mm Hg). METHODS: Intraventricular ICP was measured in a 30-degree head-up position (all patients) and in supine and 45-degree head-up positions (patients with normal ICP) during passive range of motion (comatose patients) and exercises involving limb movement (awake patients). RESULTS: In patients with normal ICP, passive range of motion decreased mean ICP by 1 mm Hg in the supine position but not in the head-up position. In patients with high ICP, it decreased ICP by 2 mm Hg. Limb exercises left the mean ICP essentially unchanged in both the patients with normal ICP and the patients with high ICP. Isometric hip adduction increased mean ICP by 4 mm Hg in patients with normal ICP. It did not affect ICP in patients with high ICP. Limb movement was associated with suppression of abnormal ICP waves and improvement of consciousness in 13 patients. CONCLUSION AND DISCUSSION: Physical therapy can be used safely in patients with normal or increased ICP provided that Valsalva-like maneuvers are avoided. [Brimioulle S, Moraine J-J, Norrenberg D, Kahn RJ. Effects of positioning and exercise on intracranial pressure in a neurosurgical intensive care unit.

Dobutamine increases cerebral blood flow velocity and jugular bulb hemoglobin saturation in septic patients.

OBJECTIVE: To evaluate the effects of dobutamine on cerebral hemodynamics in septic patients with stable hemodynamic status. DESIGN: Open-label, prospective study. SETTING: Multidisciplinary department of intensive care in a university hospital. PATIENTS: Fourteen mechanically ventilated septic patients with altered mental status and stable hemodynamic status. INTERVENTIONS: Dobutamine infusion, in incremental doses of 2 micrograms/kg/min every 10 mins, for < or = 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Mean flow velocity in the right middle cerebral artery, as measured by transcranial Doppler, increased from 68 +/- 6 (SEM) cm/sec at baseline to 80 +/- 7 cm/sec (p < .001) with 10 micrograms/kg/min of dobutamine. Cerebral arterial-venous oxygen content difference and cerebral oxygen extraction ratio concurrently decreased from 4.1 +/- 0.2 to 3.4 +/- 0.3 mL/dL (p < .05) and from 46 +/- 3% to 36 +/- 4% (p < .05), respectively. Dobutamine also increased cardiac index from 3.8 +/- 0.3 to 6.3 +/- 0.5 L/min/m2 (p < .001) and systemic oxygen delivery (DO2) from 497 +/- 35 to 817 +/- 55 mL/min/m2. Mean arterial pressure increased slightly from 77 +/- 3 mm Hg to a maximum value of 86 +/- 4 mm Hg (p < .05). Relative changes in mean flow velocity were better correlated with cardiac index (r2 = .52, p < .001) than with arterial pressure (r2 = .20; p < .001). Cerebral DO2 (estimated by the product of mean flow velocity and arterial oxygen content) increased by 12% with dobutamine, whereas estimated cerebral oxygen consumption (VO2) did not. CONCLUSION: These measurements of middle cerebral artery flow velocity and jugular bulb oximetry suggest that dobutamine increases cerebral blood flow but not cerebral VO2 in stable septic patients.

Incentive spirometry performance. A reliable indicator of pulmonary function in the early postoperative period after lobectomy?

OBJECTIVES: The purpose of our study was to validate the incentive spirometry (IS) as a simple mean to follow pulmonary function at the bedside after lung surgery. MATERIALS AND METHODS: We studied prospectively 19 patients (16 men, 3 women; mean +/- SE age, 60 +/- 2.8 years) undergoing lobectomy for lung cancer. All the patients had an obstructive pattern with FEV1/FVC below 75%. Lung volumes, including functional residual capacity (FRC) and residual volume (RV), measured using spirometry and the helium dilution technique, and IS were measured preoperatively and postoperatively at days 1, 2, 3, and 8, and at 2 months. RESULTS: Our results showed that in the postoperative period after lung resection, IS performance was well correlated (R) during the first 8 postoperative days with vital capacity (VC) (R between 0.667 and 0.870) mainly due to the excellent correlation with the inspiratory reserve volume (IRV, R between 0.680 and 0.895) but was poorly correlated with expiratory reserve volume (R below 0.340), RV (R below 0.180), and FRC (R below 0.470). CONCLUSIONS: IS can be used as a simple mean to follow lung function, especially VC and IRV, in the postoperative period in spontaneously breathing patients. IS is noninvasive and can be performed repeatedly at the bedside in the intensive care setting.

Blood interleukin 10 levels parallel the severity of septic shock.

PURPOSE: The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF alpha), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure. PATIENTS AND METHODS: In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study. RESULTS: The APACHE II score was 21 +/- 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = -0.73, P < .05) and CH50 (r = -0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (> 60 pg/mL) had lower C3 (37 +/- 11 v 62 +/- 10 mg/dL) and CH50 (32 +/- 7 v 68 +/- 19%), and higher organ failure scores (5.7 +/- 0.8 v 3.8 +/- 1.3) than those with low IL-10 levels (all P < .05). CONCLUSION: Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.

Oxygenation improvement with nitric oxide in right-to-left shunt without significant effects on pulmonary arterial pressure.

Following surgical closure of an interventricular communication complicating an anterior myocardial infarction, a 74-year-old woman developed severe right ventricular failure and hypoxemia due to the opening of a patent foramen ovale (PFO). Mean pulmonary artery pressure was 24 mm Hg. Treatment with inhaled nitric oxide (5 ppm) increased PaO2 from 47 to 90 mm Hg (FIo(2)1). The present observation points out that nitric oxide inhalation could be useful in the management of severe hypoxemia from a right-to-left shunt due to a PFO even when there is no significant pulmonary hypertension present.

Estimation of cerebral blood flow at bedside by continuous jugular thermodilution.

The Kety-Schmidt technique can be regarded as the reference method for the measurement of cerebral blood flow (CBF). However, the method is somewhat cumbersome for routine use in the intensive care unit (ICU) at the beside. The continuous thermodilution technique developed many years ago for the measurement of coronary sinus blood flow can be applied for the measurement of jugular blood flow (JBF). However, the measurement of JBF by thermodilution has never been validated using the Kety-Schmidt reference method. We first validate the continuous thermodilution in vitro by comparison with a volumetric flow. The thermodilution method is accurate for flows between 50 and 900 ml min-1 with a mean difference volumetric-thermodilution flow of -1 +/- 18 ml min-1 (mean +/- SD), and precise with a coefficient of variability ranging between 1.21% and 2.50%. In vivo accuracy was assessed by comparing in 15 comatose patients CBF measured using the Kety-Schmidt (CBFKS) method and estimated from JBF measured by thermodilution (CBFTH) at four levels of arterial PaCO2 (25, 30, 35, and 40 mm Hg). The mean difference CBFKS-CBFTH is -0.9 +/- 3.6 ml min-1 100 g-1. In vivo precision of the method was good, with a coefficient of variability of 4.1% in mean. We conclude that jugular continuous thermodilution technique is a reliable method for estimating CBF at the bedside. This technique allows repeated measurements jugular bulb blood sampling for brain metabolic studies.

Blood lactate levels are better prognostic indicators than TNF and IL-6 levels in patients with septic shock.

OBJECTIVE: Both serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) and blood lactate levels in patients with septic shock have been shown to correlate with prognosis. The aim of the study was to define the relative predictive value of these measures. PATIENTS: 38 hospitalized patients with septic shock, including 18 survivors and 20 non-survivors. INTERVENTION: Blood TNF alpha (immunoradiometric assay), IL-6 (bioassay) and lactate (enzymatic method) levels were serially measured at the onset of septic shock and after 24 and 48 h. RESULTS: TNF alpha levels tended to be higher in the non-survivors than in the survivors at the onset of shock (204 +/- 392 vs 129 +/- 195 pg/ml, p = NS) but decreased similarly in both groups with time (p = 0.03). IL-6 levels at admission were highly variable (9656 +/- 19851 U/ml in the non-survivors and 69,222 +/- 248,804 U/ml in the survivors). Log IL-6 decreased similarly in both groups with time (p = 0.004). Admission blood lactate levels were higher in the non-survivors than in the survivors (6.11 +/- 4.78 mEq/l vs 3.49 +/- 2.00 mEq/l, p < 0.05) and decreased significantly with time in all patients (p = 0.024). However, this decrease was greater in the survivors than in the non-survivors (p = 0.003). CONCLUSION: These data indicate that the large variability in TNF alpha and IL-6 levels limit their prognostic significance in patients with septic shock. The predictive value of the trend in cytokine levels over time is not superior to that of trends in blood lactate levels.

Serial blood lactate levels can predict the development of multiple organ failure following septic shock.

BACKGROUND: Despite successful initial resuscitation, septic shock frequently evolves into multiple system organ failure (MSOF) and death. Since blood lactate levels can reflect the degree of cellular derangements, we examined the relation between serial blood lactate levels and the development of MSOF, or mortality, in patients with septic shock. PATIENTS AND METHODS: In 87 patients with a first episode of septic shock, we measured initial lactate (at onset of septic shock), final lactate (before recovery or death), "lactime" (time during which blood lactate was > 2.0 mmol/L, and the area under the curve (AUC) for abnormal values (above 2.0 mmol/L). These measurements were correlated with survival and organ failure and scored for four systems (ie, respiratory, renal, hepatic, and coagulation), adding to a maximal score of 8. RESULTS: Thirty-three (38%) patients survived. Of the 54 (62%) nonsurvivors, the 13 patients who died during the first 24 hours of septic shock had higher initial blood lactate levels than those who died later (mean +/- standard deviation 9.6 +/- 5.3 mmol/L versus 5.6 +/- 3.7 mmol/L, P< 0.05). The 74 patients who survived the first 24 hours of shock, were studied in more detail. On presentation, survivors had a significantly higher mean arterial pressure (76 +/- 12 mm Hg versus 63 +/- 20 mm Hg, P < 0.001) and arterial pH (7.40 +/- 0.07 versus 7.37 +/- 0.09, P< 0.05) than nonsurvivors. Although the differences in initial blood lactate levels between survivors and nonsurvivors did not reach statistical significance (4.7 +/- 2.5 mmol/L versus 5.6 +/- 3.7 mmol/L), only the survivors had a significant decrease during the first 24 hours of septic shock. The survivors had a significantly lower lactime and AUC than the nonsurvivors. The duration of lactic acidosis was the best predictor of survival (multiple regression analysis, R2 = 0.266, P <0.001), followed by age, heart rate, and mean arterial pressure. Patients with lower organ failure scores had lower initial blood lactate, lactime, and AUC. The duration of lactic acidosis was the only significant predictor of organ failure. CONCLUSIONS: In patients with septic shock, serial determinations of blood lactate levels are good predictors of the development of MSOF an death. In this respect, the duration of lactic acidosis is more important than the initial lactate value. Although a number of factors may contribute to hyperlactatemia, these observations are compatible with a direct role of prolonged tissue hypoxia in the development of complications following septic shock.

Administration of an antibody to E-selectin in patients with septic shock.

OBJECTIVES: To determine the safety and pharmacokinetics of a murine monoclonal antibody to E-selectin in patients with newly developed septic shock. DESIGN: Open-label, prospective, phase II pilot study with escalating doses of the antibody. SETTING: Intensive care unit of a 900-bed university hospital. PATIENTS: Nine patients who survived the first 24 hrs of septic shock. INTERVENTIONS: In addition to standard therapy, an intravenous bolus of a murine monoclonal antibody to E-selectin, CY1787, was given at doses of 0.1 mg/kg (n = 3), 0.33 mg/kg (n = 3), and 1.0 mg/kg (n = 3). MEASUREMENTS AND MAIN RESULTS: CY1787 was well tolerated in all patients. Signs of shock resolved in all patients, and organ failure entirely reversed in eight patients. All patients survived the 28-day follow-up. Administration of CY1787 was associated with an early and brisk increase in PaO2/FIO2 ratio (p < .001), from 146 +/- 38 mm Hg (19.5 +/- 5.1 kPa) to 205 +/- 45 mm Hg (27.3 +/- 6.0 kPa) after 2 hrs, and 250 +/- 58 mm Hg (33.3 +/- 7.7 kPa) after 12 hrs. A dose-related effect of CY1787 was suggested by an earlier weaning from catecholamine therapy and a faster resolution of organ failure in the high-dose group. Development of antimouse antibodies was documented in eight patients. CONCLUSIONS: This pilot study indicates that this antibody to E-selectin appears to be safe and may represent a promising form of therapy in septic shock.

Early hemodynamic course of septic shock.

OBJECTIVE: To assess the relative contributions of changes in vascular tone and changes in cardiac function to hemodynamic recovery from septic shock. DESIGN: Case series, observational study. SETTING: Multidisciplinary department of intensive care in an academic hospital. PATIENTS: Sixty-seven patients with septic shock (prolonged hypotension, signs of tissue hypoperfusion, signs of sepsis, suspected source of infection, or documented bacteremia). In addition to the antibiotic therapy and the removal of the source of sepsis whenever possible, each patient received intravenous fluids and vasoactive agents (dopamine, norepinephrine, and dobutamine). Each patient was also treated with mechanical ventilation. Twenty-four (36%) patients survived their intensive care unit course. INTERVENTIONS: Hemodynamic measurements were obtained at baseline, after initial resuscitation (as soon as apparent hemodynamic stability was achieved), after 12 hrs, and after 24 hrs. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in hemodynamic or oxygen-derived variables at baseline between the survivors and the nonsurvivors. During the initial resuscitation period, only the survivors demonstrated a significant increase in mean arterial pressure (from 69 +/- 17 to 82 +/- 18 mm Hg; p < .02) and left ventricular stroke work index (from 25.2 +/- 11.0 to 35.5 +/- 19.4 g.m/m2; p < .05). The increases in cardiac index and systemic vascular resistance were greater in the survivors than in the non-survivors, but the differences did not reach statistical significance. Study of the left ventricular function curves indicated an improvement of left ventricular function in the survivors but not in the nonsurvivors. CONCLUSION: An early improvement in left ventricular function is a hallmark of the survivors from septic shock.

Correlation of serial blood lactate levels to organ failure and mortality after trauma.

To define the value of serial measurements of blood lactate levels after trauma, the present study investigated the correlation between blood lactate, mortality, and organ failure in 129 trauma patients, including 100 intensive care unit (ICU) survivors and 29 ICU fatalities. On admission, injury severity score (ISS) was higher and Glasgow coma score (GCS), revised trauma score (RTS), and trauma revised ISS (TRISS) were lower in the nonsurvivors than in the survivors. Serial arterial blood lactate levels were measured on admission and at least three times a day until normalization. Both initial lactate and highest lactate levels were higher in the nonsurvivors than in the survivors. Organ failure developed in 84 (65%) of the 129 patients. Patients with organ failure had significantly lower RTS and TRISS. Initial lactate and highest lactate levels were significantly higher in patients with organ failure than without organ failure (3.4 [0.7 to 12.7] versus 2.4 [0.4 to 7.6] mEq/L and 4.1 [0.7 to 12.7] versus 2.8 [0.4 to 8.9] mEq/L, respectively, both P < .01). The duration of hyperlactatemia averaged 2.2 days in the former but 1.0 day in the latter patients (P < .01). The data therefore indicate that not only the initial or the highest lactate value but also the duration of hyperlactatemia can be correlated with the development of organ failure. These observations stress the importance of the initial resuscitation in the prevention of organ failure. Serial blood lactate measurements are reliable indicators of morbidity and mortality after trauma.

Correction of hypocalcaemia in the critically ill: what is the haemodynamic benefit?

OBJECTIVE: The prevalence of hypocalcaemia is known to be elevated in critically ill patients, but the expected benefit from calcium repletion in hypocalcaemic patients has not been well defined. The objective of the present study was therefore prospective determination of the cardiovascular response to calcium administration in critically ill patients with hypocalcaemia. PATIENTS: A total of 17 patients found to have ionized hypocalcaemia (Ca2+ < 1.05 mmol/l) from a group of 32 patients who were invasively monitored as part of their ICU management. INTERVENTION: Slow intravenous injection of 1 g of calcium chloride. MEASUREMENTS AND RESULTS: Calcium administration was followed by an increase in mean arterial pressure from 77 +/- 8 to 90 +/- 12 mmHg (P < 0.01). There was no significant change in cardiac filling pressures or heart rate. Cardiac index and systemic vascular resistance increased slightly but not significantly (from 2.67 +/- 0.92 to 2.81 +/- 1.25 1/min.m2 and from 2133 +/- 647 to 2378 +/- 817 dynes.s.cm-5 m-2, respectively). Left ventricular stroke work index increased from 23 +/- 8 to 32 +/- 13 g.m/m2 (P < 0.01). These changes were maintained for 60 min. CONCLUSIONS: The correction of hypocalcaemia can result in a significant increase in arterial pressure that can persist for at least 1 h. Despite an associated improvement in left ventricular function, cardiac index and oxygen delivery do not increase significantly.

Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock.

Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of shock severity including lactate levels (r = 0.56, p < 0.05) and correlated negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased production of tumor necrosis factor-alpha and interleukin-6 after in vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced by in vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.

Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis.

OBJECTIVE: To compare the prognostic value of blood lactate concentrations, gastric intramucosal pH, and their combination in patients with severe sepsis. DESIGN: Prospective, noninterventional study. SETTING: Medical/surgical intensive care unit of a university hospital. PATIENTS: The study included 35 consecutive patients (44 to 82 yrs) with severe sepsis as defined by fever or hypothermia (rectal temperature > 38.3 degrees or < 35.5 degrees C), tachycardia (heart rate > 100 beats/min), tachypnea (respiratory rate > 20 breaths/min) or mechanical ventilation, abnormal white blood cell count (> 10 or < 6 x 10(3) cells/mm3), hypotension (systolic arterial pressure < 90 mm Hg), and evidence of organ dysfunction (oliguria or deterioration of mental status). INTERVENTIONS: Arterial lactate concentration and intramucosal pH were measured at the time of study entry, and at 4 and 24 hrs later. Hemodynamic data and oxygen-derived variables were determined at the time of study entry and 24 hrs later. Arterial blood and balloon saline gases were also determined to obtain the pH gap (arterial pH-intramucosal pH) and the PCO2 gap (intramural PCO2-PaCO2). MEASUREMENTS AND MAIN RESULTS: Of the 35 patients, 19 survived the intensive care unit stay. At the time of study admission, 23 (66%) patients had an increased lactate concentration (> 2 mEq/L) and 26 (74%) had a low intramucosal pH (< 7.32). Initially, there were no significant differences in blood lactate concentrations between nonsurvivors and survivors (3.2 +/- 1.5 vs. 2.8 +/- 2.3 mEq/L). Lactate concentrations remained high in nonsurvivors and progressively decreased in survivors (4 hrs: 3.3 +/- 1.1 mEq/L in nonsurvivors vs. 2.2 +/- 0.9 mEq/L in survivors [p < .01]; 24 hrs: 3.5 +/- 2.0 mEq/L in nonsurvivors vs. 1.9 +/- 1.1 mEq/L in survivors [p < .05]). Intramucosal pH was lower in the nonsurvivors than in the survivors initially (7.19 +/- 0.15 in nonsurvivors vs. 7.30 +/- 0.14 in survivors [p < .05]), at 4 hrs (7.18 +/- 0.17 in nonsurvivors vs. 7.29 +/- 0.13 in survivors [p = .06]), and at 24 hrs (7.19 +/- 0.31 in nonsurvivors vs. 7.30 +/- 0.17 in survivors [p < .05]). Of the 23 patients with initially high lactate concentrations, 12 (60%) of the 20 patients with low intramucosal pH died, as compared with one (33%) of the three patients with normal intramucosal pH (p = .052). Of the 14 patients with persistently high lactate concentrations at 24 hrs, all nine (100%) patients with low intramucosal pH, but only two (40%) of five patients with normal intramucosal pH died (p < .001). No significant relationship was found between lactate or intramucosal pH and oxygen-derived variables. Intramucosal pH correlated better with gastric intramural PCO2 (r2 = .58) than with arterial bicarbonate or base deficit/excess. Intramural PCO2 was a more specific predictor of mortality than intramucosal pH. When compared with patients with normal lactate concentrations, those patients with high lactate concentrations had a higher pH gap (0.22 +/- 0.22 vs. 0.07 +/- 0.13 [p < .01]) and PCO2 gap [21.0 +/- 33.9 vs. 1.8 +/- 9.8 torr [2.79 +/- 4.5 vs. 0.24 +/- 1.34 kPa]; p < .01). CONCLUSIONS: Both lactate concentrations and intramucosal pH represent reliable prognostic indicators in severe sepsis, and their combination improves the prognostic assessment in these patients. Both variables are better prognostic indicators than oxygen-derived variables. Intramural PCO2 appears to be a more specific variable than intramucosal pH, which partially reflects systemic metabolic acidosis. Combined determinations of blood lactate concentrations and intramucosal pH or intramural PCO2 may help to predict outcome from severe sepsis.