A prospective evaluation of hemodynamic management in acute spinal cord injury patients.

STUDY DESIGN: Prospective observational study of acute spinal cord-injured (SCI) patients. OBJECTIVES: To determine how effectively mean arterial blood pressure (MAP) and spinal cord perfusion pressure (SCPP) are maintained at target levels in acute SCI patients. SETTING: Single-institution study at a Canadian level-one trauma center. METHODS: Twenty-one individuals with cervical or thoracic SCI were enrolled within 48 h of injury. A lumbar intrathecal drain was inserted for monitoring intrathecal cerebrospinal fluid pressure (ITP). The MAP was monitored concurrently with ITP, and the SCPP was calculated. Data was recorded hourly from the time of first assessment until at least the end of the 5th day post injury. RESULTS: All subjects had at least one recorded episode with a MAP below 80 mm Hg, and 81% had at least one episode with a MAP below 70 mm Hg. On average, subjects with cervical injuries had 18.4% of their pressure recordings below 80 mm Hg. Subjects with thoracic cord injuries had on average 35.9% of their MAP recordings <80 mm Hg. CONCLUSION: It is common practice to establish MAP targets for optimizing cord perfusion in acute SCI. This study suggests that even in an acute SCI referral center, when prospectively scrutinized, the actual MAP may frequently fall below the intended targets. Such results raise awareness of the vigilance that must be kept in the hemodynamic management of these patients, and the potential discrepancy between routinely setting target MAP according to 'practice guidelines' and actually achieving them.

Paralysis in the critically ill: intermittent bolus pancuronium compared with continuous infusion.

OBJECTIVES: To compare recovery times from neuromuscular blockade between two groups of critically ill patients in whom pancuronium was administered by continuous infusion or intermittent bolus injection. To compare the mean pancuronium requirements (milligrams per kilogram per hour) and to assess the incidence of prolonged recovery times (>12 hrs) and residual muscle weakness. DESIGN: Prospective, observational cohort. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: A total of 30 mechanically ventilated patients who required pharmacologic paralysis. Patients were excluded if they had renal failure (creatinine clearance <30 mL/min), heart rate >130 beats/min, hepatic failure, peripheral nerve disease or myopathy, stroke, spinal cord damage, or myasthenia gravis. INTERVENTIONS: Patients were assigned to receive pancuronium either by continuous infusion (n = 14) or intermittent bolus (n = 16). Depth of paralysis was titrated to maintain one or two responses to Train-of-Four stimulation with an accelerograph and desired clinical goals. Recovery time was defined as time from discontinuation of muscle relaxant until the amplitude of the fourth twitch, measured every 15-30 min using an accelerograph, was 70% the amplitude of the first twitch (Train-of-Four > or = 0.7). MEASUREMENTS AND MAIN RESULTS: These patients included the only three patients with status asthmaticus in our study. The groups were similar with respect to age, sex, weight, Acute Physiology and Chronic Health Evaluation II score, mode of ventilation, creatinine clearance, indications for paralysis, and duration of pancuronium administration. The median time for patients to recover from paralysis was 3.5 hrs (95% confidence interval, 1.82-5.18) in the infusion group vs. 6.3 hrs (95% confidence interval, 3.40-9.19) in the intermittent bolus group (p = .10). Less drug was administered in the intermittent group (mean, 0.02+/-0.01 mg/kg/hr) than by infusion (mean, 0.04+/-0.01 mg/kg/hr; p < .001). Six patients (five in the infusion group and one in the intermittent group) developed persistent severe muscle weakness. In addition, six different patients (three from each group) had prolonged recovery >12 hrs. CONCLUSIONS: Our study suggests that recovery time after paralysis with continuous infusion is faster than that after intermittent bolus injection. Although more pancuronium was administered in the continuous-infusion group, recovery time was not prolonged as a consequence. It is uncertain whether pancuronium given by infusion increases the risk of persistent muscle weakness.

Does increasing oxygen delivery improve outcome in the critically ill? No.

The strategy of treating critically ill patients by increasing oxygen delivery and consumption to values previously observed among survivors of critical illness (supranormal values) is based on the belief that (1) tissue hypoxia may persist in critically ill patients despite aggressive early resuscitation to traditional endpoints of adequate tissue perfusion and (2) that increasing oxygen delivery can reverse tissue hypoxia. This article addresses the question of whether increasing oxygen delivery improves outcomes in critically ill patients by reviewing the relationship between whole-body oxygen delivery and consumption and by critically examining the randomized controlled trials that have increased oxygen delivery to supranormal values.

Decreasing frequency but worsening mortality of acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVE: To describe changes in incidence and outcome of acute respiratory failure (ARF) due to AIDS-related Pneumocystis carinii pneumonia (PCP) at a tertiary care center over the 4-year period starting April 1, 1987 with reference to previously reported data from the preceding 6 years. METHODS: All patients admitted to St. Paul's hospital with a diagnosis of AIDS-related PCP during the study period were reviewed with regard to diagnostic, clinical, therapeutic, and outcome variables. RESULTS: A total of 456 episodes of PCP were diagnosed during the study period. These were compared against 127 cases diagnosed between 1981 and 1987. The frequency of hospitalization for PCP decreased to 78% in 1987 to 1991 from 100% in 1981 to 1987 (p < or = 0.001). A similar decreasing trend was observed with regard to the incidence of PCP-related ARF that declined from 21% in 1981 to 1987 to 9% in 1987 to 1991 (p = 0.009). Despite this, overall PCP-related mortality remained stable at 12% in 1981 to 1987 and 9% in 1987 to 1991 (p = 0.26). The proportion of patients with PCP-related ARF who received mechanical ventilation decreased from 89% in 1981 to 1987 to 64% in 1987 to 1991 (p < 0.001). Despite this, the case fatality rate among mechanically ventilated patients increased from 50% in 1981 to 1987 to 89% in 1987 to 1991 (p = 0.003). These changes were associated with a significant change in the pattern of use of corticosteroids as adjunctive therapy for AIDS-related PCP. In 1985 to 1986, nearly 100% of patients admitted to the ICU received corticosteroids only after admission to the ICU, following the development of ARF. In contrast, in 1989 to 1990, 50% of patients were admitted to the ICU already receiving systemic corticosteroids. The rise in the proportion of patients receiving corticosteroids prior to ICU admission between these two intervals was statistically significant (p = 0.017). CONCLUSION: Our data show a decreasing frequency but a worsening mortality of ARF secondary to AIDS-related PCP. We conclude that ARF secondary to AIDS-related PCP developing despite maximal therapy, including adjunctive corticosteroids, carries a dismal prognosis.

Spontaneous pulmonary hemorrhage after thrombolytic therapy for acute myocardial infarction.

We report a case of 63-year-old man who developed massive pulmonary hemorrhage following intravenous streptokinase for acute myocardial infarction. Pulmonary hemorrhage was diagnosed by the triad of hemoptysis, a drop in hematocrit, and a new unilateral infiltrate on chest radiograph. This diagnosis was confirmed by autopsy findings. Pulmonary hemorrhage has rarely been reported following thrombolytic therapy. We believe that pulmonary hemorrhage is a rare but a potentially life-threatening complication of thrombolytic therapy and should be considered in the differential diagnosis of pulmonary infiltrates or falling hemoglobin after thrombolytic therapy for acute myocardial infarction with no obvious site of bleeding.

Blood transfusion as a cause of leucocytosis in critically ill patients.

The diagnosis of infection in the intensive care unit is confounded by the presence of non-infectious causes of leucocytosis. Unless such causes are recognised, time and effort will be spent on unnecessary investigations and treatments. In a prospective study we have shown that the transfusion of blood frequently (45/50 patients) causes an acute leucocytosis in such patients. This effect was not seen in 8 patients who received plasma. Blood transfusion should be added to the list of non-infectious causes of leucocytosis in the critically ill.

Mathematical coupling explains dependence of oxygen consumption on oxygen delivery in ARDS.

Because of potential for mathematical coupling of measurement errors in shared variables used to calculate oxygen consumption (FickVO2) and oxygen delivery (DO2), we asked whether determination of the FickVO2-DO2 relationship in individual patients with ARDS was statistically valid. We studied 17 clinically resuscitated patients with severe ARDS, measuring FickVO2, CalorimetricVO2 (using analysis of respiratory gases), and DO2 at regular intervals while DO2 was increased using an infusion of dobutamine. Overall, we found that DO2 (pre 482 +/- 143, post 616 +/- 170 ml O2/min.m2, p < 0.01) and FickVO2 (pre 130 +/- 23, post 147 +/- 24 ml O2/min.m2, p < 0.02) increased significantly with dobutamine infusion, but CalorimetricVO2 measured simultaneously did not change (pre 128 +/- 22, post 128 +/- 22 ml O2/min x m2, p = NS). In addition, unpooled weighted slope for FickVO2 versus DO2 (0.06) was significantly different from zero, but unpooled weighted slope for CalorimetricVO2 versus DO2 (0.01) was not significantly different from zero. Slopes of the FickVO2-DO2 relationship were significant for only three individual patients. Using methods by Stratton and colleagues to analyze the effect of mathematical coupling in the FickVO2-DO2 relationship, we found that in all patients the slope of measurement errors was greater than observed slope and that observed slope was greater than estimated true slope. Estimated true slope of the FickVO2-DO2 relationship in all individual patients was not significant. Therefore, we suggest that determination of the FickVO2-DO2 relationship in individual patients who are resuscitated and hemodynamically stable is most often not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydroxymalonate inhibits lactate uptake by the rabbit hindlimb.

Lactate uptake by skeletal muscle occurs under diverse conditions, including hypoxia and electrical stimulation. A possible metabolic fate of lactate in resting muscle is its conversion to pyruvate followed by carboxylation to malate in the cytosolic malic reaction. To test this hypothesis, we measured hindlimb lactate uptake in hypoxic mechanically ventilated rabbits. Rabbits were given intravenous infusions of hydroxymalonate, an inhibitor of the malic reaction (200 mM; n = 7), or normal saline (n = 7) at 1.1 ml/min. Hindlimb lactate uptake/release was calculated as femoral blood flow times the arteriovenous lactate difference. Saline or hydroxymalonate was infused continuously during sequential 30-min periods of normoxia (arterial PO2 approximately 150 Torr), hypoxemia (arterial PO2 approximately 30 Torr), and reoxygenation (arterial PO2 approximately 150 Torr). Hindlimb O2 transport decreased with hypoxemia, but O2 consumption remained unchanged in both groups. During hypoxemia there was net uptake of lactate by the hindlimb of the group given normal saline [4.5 +/- 0.9 (SE) mumol/min]. The hindlimb of the hydroxymalonate group continued to release lactate (-0.5 +/- 1.0 mumol/min). The inhibition of lactate uptake by hydroxymalonate supports the hypothesis that the malic reaction plays a major role in the metabolism of lactate by resting rabbit skeletal muscle.

No differences in hemodynamics, ventricular function, and oxygen delivery in septic and nonseptic patients with the adult respiratory distress syndrome.

OBJECTIVE: To determine whether there are differences in hemodynamics, ventricular function, oxygen delivery, and oxygen consumption between septic and nonseptic patients who have the adult respiratory distress syndrome (ARDS). DESIGN: Cohort analytic study. SETTING: Tertiary care medical and surgical intensive care unit, university hospital. PATIENTS: Eighteen septic (survivors, n = 8; nonsurvivors, n = 10) and 14 nonseptic (survivors, n = 7; nonsurvivors, n = 7) patients studied within 24 hrs of the diagnosis of ARDS. INTERVENTIONS: Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen delivery and consumption measurements. MEASUREMENTS AND MAIN RESULTS: Cardiac index, right and left ventricular ejection fractions, end-diastolic volume indices, oxygen delivery, and oxygen consumption were measured. There were no differences in mean systemic and pulmonary arterial pressures, cardiac index, systemic vascular resistance, right and left ventricular ejection fractions, end-diastolic volumes, and oxygen delivery and consumption between septic and nonseptic patients. CONCLUSIONS: Early in the course of ARDS, there were no differences in hemodynamics, ventricular function, and oxygen delivery and consumption between septic and nonseptic patients. Sepsis does not account for the previously reported differences in hemodynamics, ventricular function, and oxygen delivery and oxygen consumption between survivors and non-survivors of ARDS. We speculate that both ARDS and sepsis cause release of mediators which cause similar changes in hemodynamics, ventricular function, and oxygen delivery and consumption.

Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans.

OBJECTIVES: To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. DESIGN: Cohort analytic study, consecutive sample. SETTING: Two tertiary care medical and surgical intensive care units in university hospitals. PATIENTS: Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. METHODS AND INTERVENTIONS: The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. MAIN OUTCOME MEASURES: Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. RESULTS: In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. CONCLUSIONS: The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.

Oxygen consumption is independent of increases in oxygen delivery by dobutamine in septic patients who have normal or increased plasma lactate.

We asked whether the relationship between oxygen delivery and oxygen consumption is different between patients who have sepsis and normal (n = 6) or increased (n = 8) concentrations of plasma lactate. We determined oxygen consumption using analysis of respiratory gases while increasing oxygen delivery using a dobutamine infusion. The relationship between oxygen delivery and consumption was y = 124 + 0.043 * x in the normal lactate group and y = 131 - 0.003 * x in the high lactate group (95% CI for differences in slopes, -0.003 to 0.096; p < or = 0.05 for slope, normal versus high lactate). In the normal lactate group, direct oxygen consumption increased by only 8 +/- 6 ml/min/m2 after dobutamine infusion (from 144 +/- 26 to 153 +/- 22 ml/min/m2, p < or = 0.02) despite an average increase of 220 +/- 80 ml/min/m2 in oxygen delivery (from 446 +/- 91 to 666 +/- 90 ml/min/m2, p < or = 0.01). The oxygen extraction ratio fell from 0.27 +/- 0.03 to 0.21 +/- 0.02 after dobutamine (p < or = 0.017). In the high lactate group, direct oxygen consumption decreased by 1 +/- 6 ml/min/m2 after dobutamine (from 131 +/- 33 to 130 +/- 35 ml/min/m2, p > 0.60) despite an average increase of 168 +/- 138 ml/min/m2 in oxygen delivery (from 467 +/- 194 to 635 +/- 300 ml/min/m2, p < or = 0.01). The oxygen extraction ratio fell from 0.30 +/- 0.14 to 0.26 +/- 0.12 after dobutamine (p < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP.

OBJECTIVE: To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). METHODS: All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. RESULTS: A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. CONCLUSIONS: The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients.

Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome.

We asked whether oxygen consumption is dependent on oxygen delivery in 17 patients who had severe adult respiratory distress syndrome (ARDS), 10 of whom had increased concentrations of plasma lactate. We determined oxygen consumption using analysis of respiratory gases while increasing oxygen delivery using blood transfusion. Oxygen consumption did not change after transfusion (from 227 +/- 83 to 225 +/- 82 ml/min, p less than or equal to 0.38). Oxygen delivery increased from 1,043 +/- 468 ml/min (24%, p less than or equal to 0.001). Even in the 10 patients who had increased concentration of plasma lactate and metabolic acidosis, oxygen consumption remained constant after increasing oxygen delivery (pretransfusion, 224 +/- 101 ml/min; post-transfusion, 225 +/- 99 ml/min; p less than or equal to 0.83). These data have more than 99% power of detecting a change in oxygen consumption of 20 ml/min after transfusion. Therefore, we conclude that directly measured oxygen consumption remains constant and independent of increases in oxygen delivery in our patients with severe ARDS. Because simultaneously determined oxygen consumption calculated from variables shared with the calculation of oxygen delivery yielded a dependent relationship, we speculate that finding dependence of calculated oxygen consumption on oxygen delivery may be the result of methodologic error.

Pathologic dependence of oxygen consumption on oxygen delivery in acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.

Oxygen consumption is pathologically dependent on oxygen delivery in ARDS and sepsis. We asked whether oxygen consumption is dependent on oxygen delivery in severe acute respiratory failure secondary to AIDS-related PCP. In five patients who had AIDS-related PCP, diffuse bilateral pulmonary infiltrates, no evidence of bacterial infection, and acute respiratory failure requiring mechanical ventilation with arterial oxygen tensions less than 75 mm Hg while breathing at least 50 percent oxygen, and PEEP greater than 10 cm H2O, we determined oxygen delivery and consumption by calculation from thermodilution cardiac output and arterial and mixed venous oxygen contents. Oxygen delivery was increased using transfusion of two units of packed red blood cells over one hour. Oxygen delivery increased 22 percent (638 +/- 204 to 778 +/- 201 ml/min.m2, p less than or equal to 0.006). Oxygen consumption increased 11 percent (134 +/- 34 to 149 +/- 29 ml/min.m2, p less than or equal to 0.02). The oxygen extraction ratio did not change. We conclude that similar to ARDS and sepsis, oxygen consumption may be pathologically dependent on oxygen delivery in patients who have severe acute respiratory failure secondary to AIDS-related PCP.

Physiologic effects and side effects of prostaglandin E1 in the adult respiratory distress syndrome.

Because PGE1 previously has been reported to increase survival of patients with ARDS, we evaluated physiologic effects and side effects of PGE1 in a prospective open-label study of patients with ARDS. Seventeen patients with ARDS who did not have significant renal or hepatic dysfunction received PGE1 by continuous central venous infusion (30 ng/kg/min). Seventeen control patients with ARDS without renal or hepatic dysfunction who had similar APACHE II and ARDS scores and causes of ARDS did not receive PGE1. Prostaglandin E1 significantly decreased the SVRI and oxygen extraction ratio. Concentrations of total and polymorphonuclear leukocytes, but not platelets, increased significantly during PGE1 infusion, but did not change in control patients. There was no change in the Do2I and Vo2I during the course of the PGE1 infusion. There were no differences in Do2I and Vo2I during PGE1 infusion between survivors and nonsurvivors. Prostaglandin E1 was infused for a mean of 5.9 +/- 1.8 days (+/- SD) and was discontinued on ten occasions in seven patients because of supraventricular dysrhythmias (n = 4), hypotension (n = 3), thrombocytopenia (n = 3), and cardiac arrest (n = 2). Nonsurvivors had PGE1 discontinued prematurely more frequently than survivors (56 percent [5/9] vs 25 percent [2/8], respectively). The prevalence of multiple-system organ failure and the in-hospital mortality of both PGE1-treated and control patients were not different. Although PGE1 causes significant systemic vasodilation and possibly decreased intrapulmonary polymorphonuclear leukocyte sequestration, PGE1 does not influence multiple-system organ failure or mortality of patients with ARDS without renal or hepatic dysfunction.

Oxygen delivery and consumption and ventricular preload are greater in survivors than in nonsurvivors of the adult respiratory distress syndrome.

In patients with adult respiratory distress syndrome (ARDS), oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Because of alterations in ventricular function, DO2 may be inadequate to satisfy oxygen demand and may contribute to multiple-system organ failure (MSOF). To determine whether there are differences in DO2, VO2, ventricular function, and MSOF, between survivors and nonsurvivors of ARDS, we studied 29 patients without cardiac disease early in the course of ARDS (hypoxemia, diffuse bilateral pulmonary infiltrates, and pulmonary artery occlusion pressure less than 18 mm Hg). Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen transport measurements were made within 24 h of onset of ARDS. Thirteen survivors had greater DO2 and VO2 than did 16 nonsurvivors (p = 0.004 and 0.001, respectively). MSOF developed in no survivors and in 63% of nonsurvivors. In four survivors and in six nonsurvivors in whom DO2 was changed acutely, VO2 was dependent on DO2 (p = 0.014). Survivors had greater stroke volume index and right and left ventricular end-diastolic volume indices than did nonsurvivors despite similar right atrial and pulmonary artery occlusion pressures. There were no differences between survivors and nonsurvivors in biventricular ejection fractions. We conclude that survivors of ARDS have greater DO2 and VO2 than do nonsurvivors. Survival may be explained by the strong inverse relation between DO2 and development of MSOF.(ABSTRACT TRUNCATED AT 250 WORDS)