Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery

OBJECTIVE: To describe and compare procalcitonin (PCT) concentrations after cardiac surgery in uncomplicated patients and in patients with perioperative myocardial infarction (PMI). DESIGN: Retrospective comparative study. SETTING: One university hospital. PATIENTS: Fifty-eight adult patients undergoing cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In a first step, plasma PCT and C-reactive protein concentrations were measured preoperatively and until 72 hrs postoperatively in ten consecutive patients who underwent uncomplicated cardiac surgery. PCT concentrations increased progressively from the end of cardiopulmonary bypass (0.09 +/- 0.09 ng/mL), peaked at 24 hrs postoperatively (1.14 +/- 1.24 ng/mL), and began to decrease at 48 hrs. C-reactive protein appeared to peak at 48 hrs (from 5.8 +/- 11.7 mg/L preoperatively to 265.1 +/- 103.5 mg/L on the second postoperative day). In a second step, PCT concentrations were measured at day one in 23 patients (PMI group) who presented high postoperative plasma cardiac troponin I concentrations and were compared with PCT concentrations observed in 25 matched uncomplicated patients. All patients were free from infection. PCT in the PMI group was significantly higher than in the control group (27.1 +/- 63.2 vs. 2.0 +/- 2.4 ng/mL, respectively; p =.0053). CONCLUSION: Because high plasma concentrations of PCT were found in patients with PMI after cardiac surgery, it may be suggested that, in the early postoperative period, elevated plasma PCT concentrations should be interpreted with caution regarding infection diagnosis.     

Changes in biochemical and biophysical surfactant properties with cardiopulmonary bypass in children

OBJECTIVE: The aim of the present study was to characterize pulmonary surfactant properties in children undergoing cardiovascular surgery with cardiopulmonary bypass. DESIGN: Prospective clinical trial. SETTING: University hospital pediatric intensive care unit. PATIENTS: Fifty pediatric patients with congenital cardiac defects undergoing cardiovascular surgery with (n = 35) and without (n = 15) cardiopulmonary bypass procedure. INTERVENTIONS: Tracheal aspirates were collected by saline lavage during routine suctioning before (baseline) and after cardiopulmonary bypass, as well as 4, 8, and 24 hrs after admission to the pediatric intensive care unit. MEASUREMENTS AND MAIN RESULTS: Total protein and phospholipid concentrations were assessed in native tracheal aspirates, in large surfactant aggregates, and in small surfactant aggregates. Phospholipid profiles and phosphatidylcholine fatty acids; surfactant apoproteins SP-A, SP-B, and SP-C (enzyme-linked immunosorbent assay); and surface activity (Pulsating Bubble Surfactometer) were all analyzed in large surfactant aggregates. With cardiopulmonary bypass, an initial increase in total protein content was followed by an increase in phospholipid concentration in tracheal aspirates. Large surfactant aggregates decreased 4 hrs after cardiopulmonary bypass (4 hrs, 22.6 +/- 5.6%; mean +/- SEM; p<.01 compared with baseline, 55.4 +/- 9.2%) but recovered within 24 hrs. The phospholipid-protein ratio of large surfactant aggregates 24 hrs after cardiopulmonary bypass (1.2 +/- 0.2; p<.01) was significantly decreased compared with baseline (2.9 +/- 0.6). The relative amount of phosphatidylglycerol content in the large surfactant aggregates-fraction dropped linearly over time but other phospholipids remained mainly unchanged. Phosphatidylcholine fatty acid profiles remained unaffected by cardiopulmonary bypass. The relative content of SP-B and SP-C in large surfactant aggregates increased approximately three-fold compared with baseline. Altogether, our findings with recovered large surfactant aggregate/small surfactant aggregate ratios and increased phospholipid in tracheal aspirates after 24 hrs represent an approximately ten-fold increase in large surfactant aggregate-associated SP-B and SP-C compared with baseline. Only minor changes were detected in biophysical properties of large surfactant aggregates throughout the observation period. CONCLUSIONS: Cardiopulmonary bypass procedure in children induces profound changes in the surfactant system involving both phospholipid and protein components; biophysical function may have been maintained by compensatory increase in SP-B and SP-C.     

Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass

OBJECTIVE: We previously demonstrated that dexamethasone treatment before cardiopulmonary bypass in children reduces the postoperative systemic inflammatory response. The purpose of this study was to test the hypothesis that dexamethasone administration before cardiopulmonary bypass in children correlates with a lesser degree of myocardial injury as measured by a decrease in cardiac troponin I release. DESIGN: A prospective, randomized, double-blind study. SETTING: The cardiac surgery operating room and intensive care unit of a pediatric referral hospital. SUBJECTS: Twenty-eight patients who underwent open-heart surgery for congenital heart defects. INTERVENTIONS: Patients received either placebo (group I, n = 13) or dexamethasone, 1 mg/kg iv (group II, n = 15), 1 hr before initiation of cardiopulmonary bypass. Plasma cardiac troponin I samples were obtained at three time points: immediately before study agent (sample 1), 10 mins after protamine sulfate administration after cardiopulmonary bypass (sample 2), and 24 hrs postoperatively (sample 3). MEASUREMENTS AND MAIN RESULTS: Mean cardiac troponin I levels (+/-sd) were significantly lower at sample time 3 in group II (dexamethasone; 33.4 +/- 20.0 ng/mL) vs. group I (control; 86.9 +/- 81.1) (p =.04). CONCLUSION: Dexamethasone administration before cardiopulmonary bypass in children resulted in a significant decrease in cardiac troponin I levels at 24 hrs postoperatively. We postulate that this may represent a decrease in myocardial injury, and, thus, a possible cardioprotective effect produced by dexamethasone.     

Cortisol antiinflammatory effects are maximal at postoperative plasma concentrations

OBJECTIVE: To determine the plasma concentration of cortisol that is needed for maximal suppression of the systemic inflammatory response to cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind clinical study of cardiac surgical patients. SETTING: Operating room and inpatient care facility of a university medical center. SUBJECTS: Sixty elective cardiac surgical patients scheduled for coronary artery bypass graft, cardiac valve replacement, or both. INTERVENTIONS: Patients were randomized to receive one of three different hydrocortisone doses, by intravenous infusion, for 6 hrs before, during, and immediately after surgery while also receiving etomidate to suppress endogenous cortisol production. MEASUREMENTS AND MAIN RESULTS: Serial determinations of plasma interleukin-6 were studied as a marker of systemic inflammation. Measurements of interleukin-10 were used as a marker of the compensatory antiinflammatory response. Plasma cortisol concentrations in an untreated control group rose from 17 microg/dL before surgery to a mean of 43 microg/dL by 4 hrs after surgery. A dose of hydrocortisone (4 microg/kg/min for 6 hrs) that maintained plasma cortisol between 40 and 50 microg/dL, starting 60-90 mins before surgery, significantly suppressed plasma interleukin-6 after surgery compared with control while significantly increasing plasma interleukin-10 during surgery. Plasma interleukin-6 after surgery was not suppressed further by increasing the dose of hydrocortisone to 8 microg/kg/min, although the mean peak plasma interleukin-10 concentration increased further compared with the group that received the 4 microg/kg/min hydrocortisone dose. CONCLUSIONS: At the doses studied, cortisol-induced suppression of plasma interleukin-6 during and after cardiac surgery appears to be a saturable phenomenon at the concentration of plasma cortisol that is normally achieved after surgery in untreated patients.     

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.     

Pharmacokinetics of methohexital during cardiovascular surgery with cardiopulmonary bypass

The pharmacokinetics of methohexital after intravenous bolus administration was studied during cardiovascular surgery with cardiopulmonary bypass. The effect of body temperature (normothermia and hypothermia) during cardiopulmonary bypass on methohexital pharmacokinetics was investigated. The pharmacokinetic data obtained were compared with those from vascular surgery without cardiopulmonary bypass. A marked decrease in plasma methohexital concentrations and therefore in area under curve and a significant increase in clearance and in volume of distribution were observed in the cardiopulmonary bypass groups compared to the vascular surgery group without cardiopulmonary bypass. However, the elimination half-life and the mean residence time were similar in the 2 groups. Furthermore, the study shows that body temperature during cardiopulmonary bypass does not influence methohexital pharmacokinetics.     

Neutrophils and platelets accumulate in the heart, lungs, and kidneys after cardiopulmonary bypass in neonatal pigs

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass elicits a systemic inflammatory response. An exaggerated response is associated with organ dysfunction and increased morbidity and mortality. DESIGN: The aim of the present study was to investigate whether the cardiopulmonary bypass procedure in itself results in accumulation of isotope-labeled platelets, polymorphonuclear neutrophils, and fibrinogen at organ levels in neonatal pigs and to monitor changes in organ function. SETTING: Pediatric cardiopulmonary bypass setup with 60 mins of aortic cross-clamp time and 120 mins of hypothermic cardiopulmonary bypass time. SUBJECTS: Thirty piglets were allocated to sternotomy alone (sham group, n = 15) or to sternotomy and cardiopulmonary bypass (n = 15). MEASUREMENTS AND MAIN RESULTS: Isotope-labeled autologous polymorphonuclear neutrophils, platelets, and commercially available fibrinogen were infused, and the specific accumulation at organ level was measured in a gamma counter 4 hrs after termination of cardiopulmonary bypass. Concomitant changes in oxygenation index and cardiac output were registered. Animals exposed to cardiopulmonary bypass showed a significantly higher technetium-99m-polymorphonuclear neutrophil accumulation in the lungs and kidneys, whereas indium-111-platelets accumulated in the heart and kidneys compared with the sham group. There was a significantly larger increase in oxygenation index and significantly larger decrease in cardiac output between the pre- and postcardiopulmonary bypass period in the cardiopulmonary bypass group compared with the sham group. CONCLUSIONS: The cardiopulmonary bypass procedure without cardiac surgery elicits organ dysfunction in terms of impaired respiratory and hemodynamic function. Platelets and polymorphonuclear neutrophils were entrapped in the heart, lungs, and kidneys of cardiopulmonary bypass animals, indicating that cell accumulation may contribute to the developing organ dysfunction.     

Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery

OBJECTIVES: Systemic inflammatory response occurs frequently after coronary artery bypass surgery, and it is strongly correlated with the risk of postoperative morbidity and mortality. Recent studies demonstrate that treatment with statin is associated with a significant and marked decrease in inflammation-associated variables such as the C-reactive protein, cytokines, and adhesion molecules. Therefore, we investigated the effects of preoperative atorvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass. DESIGN: Double-blinded, placebo-controlled, randomized study. SETTING: University hospital. PATIENTS: Forty patients were randomized to treatment with atorvastatin (20 mg/day, group A, n=20) or placebo (group B, n=20) 3 wks before surgery. INTERVENTIONS: Three-week treatment by atorvastatin 20 mg/day. MEASUREMENT AND MAIN RESULTS: Postoperative serum levels of both interleukin-6 and interleukin-8 increased significantly over baseline, but the peak levels observed 4 hrs postoperatively were significantly lower in the atorvastatin group. In the same fashion, CD11b expression on neutrophils was significantly lower in the statin group at 4 and 24 hrs postoperatively. Finally, neutrophil-endothelial adhesion was significantly reduced in the statin patients compared with controls. The operation time, blood loss, need for inotropic support, intubation time, and length of intensive care unit or hospital stay did not differ significantly between the two groups. The systemic inflammatory response syndrome score on postoperative days 1 and 2 was comparable in both groups. CONCLUSIONS: Pretreatment with atorvastatin significantly reduces cytokine release and neutrophil adhesion to the venous endothelium in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.     

Hyperlactatemia during cardiopulmonary bypass: determinants and impact on postoperative outcome

Introduction  

Hyperlactatemia during cardiopulmonary bypass is relatively frequent and is associated with an increased postoperative morbidity. The aim of this study was to determine which perfusion-related factors may be responsible for hyperlactatemia, with specific respect to hemodilution and oxygen delivery, and to verify the clinical impact of hyperlactatemia during cardiopulmonary bypass in terms of postoperative morbidity and mortality rate.     

Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans

OBJECTIVE: Animal studies have demonstrated that reperfusion disorders occurring after cardiac arrest affect outcome. Reperfusion injury can be caused by activation of complement, polymorphonuclear leukocytes (PMN), and PMN-endothelial interaction. We studied different specific markers of these processes during and after cardiopulmonary resuscitation in humans. DESIGN: Prospective clinical trial. SETTING: University hospital. PATIENTS: A total of 55 patients who underwent out-of-hospital cardiopulmonary resuscitation for nontraumatic causes. INTERVENTIONS: Blood samples were drawn immediately, 15 mins, and 30 mins after initiation of cardiopulmonary resuscitation. In the case of restoration of spontaneous circulation, additional blood samples were taken at serial time points until 7 days after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: A marked activation of complement and PMN was found in all patients investigated. Serum concentrations of specific activation markers of the complement system, anaphylatoxin C3a and the soluble membrane attack complex SC5b-9, and PMN elastase were increased during cardiopulmonary resuscitation and for 相似文献   

Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery

OBJECTIVE: Severe systemic inflammation with a vasodilatory syndrome occurs in about one third of all patients after cardiac surgery with cardiopulmonary bypass. Hydrocortisone has been used successfully to reverse vasodilation in septic patients. We evaluated if stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass. DESIGN: Randomized, nonblinded, controlled trial. SETTING: Anesthesiologic intensive care unit for cardiac surgical patients of an university hospital. PATIENTS: After a risk analysis, we enrolled 91 patients into a prospective randomized trial. Patients were included according to the evaluated criteria (preoperative ejection fraction, duration of cardiopulmonary bypass, type of surgery). INTERVENTIONS: The treatment group received stress doses of hydrocortisone perioperatively: 100 mg before induction of anesthesia, then 10 mg/hr for 24 hrs, 5 mg/hr for 24 hrs, 3 x 20 mg/day, and 3 x 10 mg/day. MEASUREMENTS AND MAIN RESULTS: We measured various laboratory (e.g., lactate) and clinical variables (e.g., duration of ventilation and length of stay in the intensive care unit), characterizing the patients' outcome. The two study groups did not differ regarding age, preoperative medication, duration of the cardiopulmonary bypass, and type of surgery. The patients in the treatment group had significantly lower concentrations of IL-6 and lactate, higher antithrombin III concentration, lower need for circulatory and ventilatory support and for transfusions, lower Therapeutic Intervention Scoring System values, and shorter length of stay in the intensive care unit and in the hospital. The mortality rate did not differ significantly between the groups. CONCLUSIONS: Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome.     

Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults

OBJECTIVES: The primary objective was to evaluate the relationship between high-dose lorazepam and serum propylene glycol concentrations. Secondary objectives were a) to document the occurrence of propylene glycol accumulation associated with continuous high-dose lorazepam infusion; b) to assess the relationship between lorazepam dose, serum propylene glycol concentrations, and propylene glycol accumulation; and c) to assess the relationship between the osmol gap and serum propylene glycol concentrations. DESIGN: Prospective, observational study. SETTING: Tertiary care, medical intensive care unit. PATIENTS: Nine critically ill adults receiving high-dose lorazepam (> or =10 mg/hr) infusion. INTERVENTIONS: Cumulative lorazepam dose (mg/kg) and the rate of infusion (mg.kg(-1).hr(-1)) were monitored from initiation of lorazepam infusion until 24 hrs after discontinuation of the high-dose lorazepam infusion. Serum osmolarity was collected at 48 hrs into the high-dose lorazepam infusion and daily thereafter. Serum propylene glycol concentrations were drawn at 48 hrs into the high-dose lorazepam infusion, and the presence of propylene glycol accumulation, as evidenced by a high anion gap (> or =15 mmol/L) metabolic acidosis with elevated osmol gap (> or =10 mOsm/L), was assessed at that time. MEASUREMENTS AND MAIN RESULTS: The mean cumulative high-dose lorazepam received and mean high-dose lorazepam infusion rate were 8.1 mg/kg (range, 5.1-11.7) and 0.16 mg.kg(-1).hr (-1)(range, 0.11-0.22), respectively. A significant correlation between high-dose lorazepam infusion rate and serum propylene glycol concentrations was observed (r =.557, p =.021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r =.804, p =.001). Propylene glycol accumulation was observed in six of nine patients at 48 hrs. No significant correlation between duration of lorazepam infusion and serum propylene glycol concentrations was observed (p =.637). CONCLUSION: Propylene glycol accumulation, as reflected by a hyperosmolar anion gap metabolic acidosis, was observed in critically ill adults receiving continuous high-dose lorazepam infusion for > or =48 hrs. Study findings suggest that in critically ill adults with normal renal function, serum propylene glycol concentrations may be predicted by the high-dose lorazepam infusion rate and osmol gap.     

Gastric mucosal acidosis and cytokine release in patients with septic shock

OBJECTIVE: It has been postulated that in critically ill patients, splanchnic hypoperfusion may lead to cytokine release into the systemic circulation. The presence of cytokines could trigger an inflammatory response and cause multiple organ dysfunction syndrome. Although experimental studies support this hypothesis, humans studies remain controversial. The aim of the study was to determine the relationship between splanchnic hypoperfusion and cytokine release during septic shock. DESIGN: Human prospective study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: A total of 30 patients with mean arterial pressure of <60 mm Hg after volume loading with either oliguria or hyperlactatemia. MEASUREMENTS: Gastric intramucosal measurements as an indicator of splanchnic hypoperfusion and blood samples were obtained at admission to the medical intensive care unit and repeated during 48 hrs. Cytokine (tumor necrosis factor-alpha and interleukin-6) values were evaluated by enzyme-linked immunoassays at the following periods: at the time of admission and 2, 4, 8, 12, 24, 36, and 48 hrs later. MAIN RESULTS: High levels of interleukin-6 and tumor necrosis factor-alpha were observed at admission in survivors and nonsurvivors, without significant difference. At 48 hrs, cytokine levels were significantly higher in patients who died compared with the survivors (tumor necrosis factor: 163 +/- 16 for nonsurvivors vs. 34 +/- 9 ng/mL for survivors; interleukin-6: 2814 +/- 485 for nonsurvivors vs. 469 +/- 107 ng/mL for survivors). At 48 hrs, the PCO2 gap was significantly higher in the nonsurvivors compared with survivors (25.87 +/- 2.73 vs. 11.35 +/- 2.25 mm Hg), despite systemic hemodynamic variables in the normal range. A positive relationship was demonstrated between plasma levels of tumor necrosis factor-alpha and interleukin-6 and the PCO2 gap throughout the study. The PCO2 gap was not correlated with hemodynamic variables. CONCLUSIONS: Our data suggest a relationship between gastric mucosal acidosis, as assessed by PCO2 gap, and cytokine levels in critically ill patients with septic shock. Gut injury may be a contributor of the inflammatory response in patients with septic shock.     

Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass

OBJECTIVES: To examine the behavior of soluble tumor necrosis factor (TNF) receptors in circulation before and after cardiopulmonary bypass and the relationship to the development of cytokinemia and acute complications comprising systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). The predictive value of soluble TNF receptor is assessed herein. DESIGN: Prospective study comparing prebypass and postbypass levels in patients with and without complications indicative of SIRS and MODS. SETTING: Cardiac surgical intensive care unit in a tertiary care hospital. PATIENTS: A total of 20 pediatric patients who underwent cardiopulmonary bypass during open heart surgery. INTERVENTIONS: Blood samples were collected from catheters before and 2 hrs and 24 hrs after the onset of bypass. MEASUREMENTS AND MAIN RESULTS: We measured plasma levels of soluble TNF receptors by using enzyme-linked immunosorbent assay in 20 patients before and after cardiopulmonary bypass. Clinical data, including duration of bypass and tests or signs indicative of SIRS/MODS, were collected. Soluble TNF receptor I (p55 sR), significantly increased (2241 +/- 312 pg/mL) at 2 hrs after bypass (p <.0005) and remained elevated (2826 +/- 695 pg/mL) at 1 day after bypass (p <.005) when compared with prebypass levels (725 +/- 130 pg/mL). Patients with the acute complications of SIRS/MODS had a higher ratio of postbypass to prebypass p55 sR levels (5.0-fold, p <.001) when compared with patients with no SIRS/MODS (1.75-fold). Remarkably, before surgery, levels of TNF p55 sR predict both cytokinemia (r =.67 to.73, p <.05) and SIRS/MODS (p <.01). The prebypass levels of TNF p55 sR were consistently higher (range, 1000-1400 pg/mL) in patients who subsequently developed SIRS/MODS than the levels (range, 400-570 pg/mL) in patients who did not develop SIRS/MODS. Hypotension, respiratory dysfunctions, and coagulopathy were particularly more prevailing (p <.005) among the complications that were associated with high prebypass levels of TNF p55 sR. CONCLUSIONS: Soluble TNF receptor p55 can be employed as a predictive marker for cytokinemia and the development of SIRS/MODS that may arise from a major insult to the body such as cardiopulmonary bypass.     

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.     

Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care

OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass. DESIGN: A prospective, observational, clinical study. SETTING: A tertiary pediatric cardiac center. PATIENTS: Eighty-two infants and children undergoing elective cardiac surgery between March and December 1999. MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis. CONCLUSIONS: Patients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.     

Reliability of anion gap as an indicator of blood lactate in critically ill patients

Objective: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. Design: Prospective study. Setting: General intensive care unit of a university hospital. Patients: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. Measurements and results: The anion gap was calculated as [Na⁺] − [Cl⁻] − [TCO₂]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 ± 3.2 mmol/l and the mean serum anion gap was 14.3 ± 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44 % [95 % confidence interval (CI) 38 to 50], whereas specificity was 91 % (CI 87 to 94) and the positive predictive value was 86 % (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67 % (CI 58 to 75) and specificity = 83 % (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r ² = 0.41, p < 0.001) and the slope of this relationship (0.48 ± 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 ± 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 ± 7.1 mmol/l). Conclusions: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap. Received: 22 May 1996 Accepted: 13 January 1997     

Low systemic vascular resistance state in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To determine the prevalence, hemodynamic characteristics, and risk factors for the low systemic vascular resistance (SVR) state in patients who have undergone cardiopulmonary bypass. DESIGN: Prospective cohort study. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Seventy-nine consecutive patients who underwent coronary artery bypass graft, mitral valve, or aortic valve procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Low SVR was defined as an indexed systemic vascular resistance (SVRi) of <1800 dyne x sec/cm5 x m2 at two consecutive times postoperatively. SVRi, cardiac index, mean arterial pressure, temperature, and central venous pressure were recorded before bypass and at 0, 1, 2, 4, 8, and 16 hrs after bypass. We recorded age, gender, urgency of operation, use of angiotensin-converting enzyme inhibitors and calcium channel blockers, ejection fraction, pump time, cross-clamp time, use of antifibrinolytics, type of oxygenator, amrinone use, postoperative biochemical and hematologic values, medication use, fluid balance, intensive care unit admission duration, and hospital admission duration. We assessed the role of diabetes mellitus, current smoking, and systemic hypertension. The incidence of the low-SVR state was 35 of 79 patients during a 3-month period (44%). At 8 hrs postoperatively, the SVRi in low-SVR and non-low-SVR patients was 1594+/-50 (SEM) and 2103+/-56 (SEM) dyne x sec/cm5 x m2, respectively (p < .001). In low-SVR patients, there was an initial and sustained increase in cardiac index and central venous pressure that preceded the decrease in mean arterial pressure. The decrease in mean arterial pressure was maximal at 8 hrs postoperatively. Patients with low SVR were more likely to have longer cross-clamp times, to be male, and to have lower postoperative platelet counts (p < .05 for all). Low-SVR patients were less likely to require dobutamine in the first 4 hrs postoperatively. CONCLUSIONS: Low SVR, a probable manifestation of systemic inflammatory response syndrome, is common in patients after cardiopulmonary bypass. These patients may respond better to a vasopressor to restore vascular tone than to volume loading to further increase cardiac index.     

An increase in urinary nitrite/nitrate excretion is associated with the hyperdynamic state after cardiovascular surgery

OBJECTIVES: To test the hypotheses (1) that nitric oxide (NO) production is stimulated after cardiovascular surgery and is related to the hyperdynamic state and (2) that NO production is more prominent in patients with cardiopulmonary bypass. DESIGN: Prospective, clinical study. SETTING: Intensive care unit in a university hospital. PATIENTS: One hundred patients after cardiovascular surgery: coronary artery bypass graft with (n=53) and without (n=17) cardiopulmonary bypass, valve surgery with cardiopulmonary bypass (n=23) and thoracic aortic replacement with cardiopulmonary bypass (n=7). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Urinary nitrite/nitrate (NOx) excretion was measured by the high-performance liquid chromatography-Griess system as an index of endogenous NO production during the first 2 postoperative days. Hemodynamic variables, hematologic variables and serum C-reactive protein concentrations were measured after the operation. Urinary NOx concentrations were 146+/-70 and 190+/-93 micro mol/l, and the amounts of NOx excreted in the urine were 23+/-10 and 18+/-8 micro mol/h on the 1st and 2nd days, respectively. Urinary NOx excretions were positively correlated with the cardiac index (P<0.01), but inversely correlated with the systemic vascular resistance index (P<0.01). Urinary NOx concentrations were positively correlated with serum C-reactive protein concentrations (P<0.01), but inversely correlated with the cardiopulmonary bypass time (P<0.01). The urinary NOx concentration was highest in patients undergoing coronary artery bypass graft without cardiopulmonary bypass. CONCLUSION: These findings suggest, firstly, that NO production is stimulated by a surgical inflammatory response and, secondly, that the endogenous NO contributes to the increase in cardiac output that accompanies the reduced systemic vascular resistance after cardiovascular surgery.