Debate: Transfusing to normal hemoglobin levels improves outcome.

Red cells are uniquely designed to transport oxygen and facilitate oxygen uptake by systemic tissues. Blood transfusions are thus logical therapeutic choices in patients who exhibit signs of oxygen debt. A small number of studies that have addressed patients with metabolic or physiologic signs of oxygen debt or regional ischaemia suggest that liberal blood transfusion strategies improve outcome. Therefore, armed with an understanding of the variety of clinical presentations characterising oxygen debt, as well as an appreciation of the risks involved, blood transfusions should be considered in all critically ill patients. This includes the consideration of liberalized hemoglobin triggers and hemoglobin thresholds in normal ranges.

Bedside procedures. Solutions to the pitfalls of intrahospital transport.

The technology to perform diagnostic and therapeutic procedures at the bedside continues to advance. Because of documented hazards and the expense of intrahospital transport, the bedside is becoming an appealing site for procedures that are more commonly performed in radiologic, bronchoscopic, other procedural suites, and the operating room.

Cation metabolism during propofol sedation with and without EDTA in patients with impaired renal function.

OBJECTIVE: To compare the effects of propofol with and without disodium edetate (EDTA) on cation metabolism in intensive care unit (ICU) patients with renal insufficiency who received propofol or propofol plus EDTA (propofol EDTA) for sedation and mechanical ventilation. DESIGN: Double-blind, randomised, multicentre study. SETTING: Medical and surgical ICUs from 5 hospitals. PATIENTS: Thirty-nine ICU patients with acute and chronic renal impairment expected to require at least 24 hours of continuous sedation and respiratory failure necessitating mechanical ventilation. INTERVENTIONS: Propofol or propofol EDTA administered for sedation by continuous intravenous infusion. MEASUREMENTS AND RESULTS: The depth of sedation, as measured by the Modified Ramsay Sedation Scale, was similar in the 2 groups, when adjusted for dosing differences. The amount of propofol required to maintain adequate sedation was decreased in both groups compared to propofol requirements in ICU patients with normal renal function. EDTA levels were elevated at baseline in both groups. In the propofol EDTA group, the EDTA levels increased further by 20 % but decreased to below baseline EDTA levels at 48 hours after sedation. In the propofol group, EDTA levels decreased during sedation and remained below baseline levels at 48 hours after sedation. PATIENTS in both groups were hypocalcaemic and hyperphosphataemic at baseline with low levels of 1,25-dihydroxyvitamin D and elevated parathyroid hormone (PTH) levels. Other than a slight difference in ionised serum calcium levels at 4 h after the start of sedation, there were no significant differences observed in serum calcium levels between the two groups. There were no significant differences in 1,25-dihydroxyvitamin D or PTH levels over time between the two groups. There was no significant effect on renal function in either group. CONCLUSIONS: The results of this study suggest that adding EDTA to propofol does not adversely affect cation homeostasis or renal function when used for sedation of ICU patients with renal insufficiency. Although EDTA levels increased over time from baseline levels in patients with renal insufficiency who receive propofol EDTA, this increase does not appear to be clinically significant, and EDTA levels return to below baseline levels within 48 hours of discontinuing the propofol EDTA infusion. The efficacy of propofol with and without EDTA also appears comparable in these patients.

Persistent gastric intramucosal ischemia in patients with sepsis following resuscitation from shock.

STUDY OBJECTIVES: (1) To determine the effects of resuscitation of patients with severe sepsis to conventional hemodynamic end points and normal blood lactate levels on postresuscitation sequential assessments of gastric intramucosal pH (pHi). (2) To determine whether trends in pHi are reflected in trends in systemic hemodynamic, oxygen utilization, and acid-base assessments. DESIGN: Prospective cohort study. SETTING: Medical ICU in an inner-city, university-based medical center. PATIENTS: Twelve recently admitted patients with severe sepsis and signs of circulatory shock who were successfully resuscitated to normal hemodynamic end points and lactate levels and who were also monitored with pulmonary artery catheters and gastric tonometers. INTERVENTIONS: Because of the observational nature of this study, no specific interventions were employed. The physician staff administered i.v. fluids and pharmacologic agents, during and after the resuscitative period, to treat infection and to achieve and maintain hemodynamic stability. Mechanical ventilation and supplemental oxygen were provided as needed. The hemodynamic and physiologic monitoring employed was determined by the managing physicians and established medical ICU routines. MEASUREMENTS AND RESULTS: A total of 12 patients were studied. Systemic hemodynamic, oxygen utilization, and acid-base assessments and pHi were recorded following resuscitation, and every 12 h thereafter. pHi decreased from 7.33 +/- 0.08 (mean +/- SD) following resuscitation to 7.26 +/- 0.04 at 24 h, 7.20 +/- 0.07 at 36 h (p < 0.05), and 7.24 +/- 0.08 at 48 h. Corresponding statistically significant and clinically relevant changes in systemic hemodynamic, oxygen utilization, and acid-base variables were not observed. The hospital mortality of this patient group was high (10 of 12; 83%). CONCLUSIONS: Gastric intramucosal acidosis develops and persists for at least 48 h in patients resuscitated from septic shock to conventional resuscitative end points, including the normalization of lactate levels. These regional changes were not reflected in corresponding changes in systemic acid-base and oxygen utilization variables. Direct determinations of pHi and therapy directed toward the resolution of splanchnic ischemia may be required to improve the outcome in these patients.

Fluid resuscitation in patients with increased vascular permeability.

Fluid therapy is a uniformly accepted, logical, and highly effective therapeutic intervention for the treatment of patients with reductions in circulating intravascular volume. This article discusses fluid resuscitation of shock associated with increased vascular permeability and addresses the use of colloids and crystalloids in these disorders.

Hemodynamic responses to gram-positive versus gram-negative sepsis in critically ill patients with and without circulatory shock.

OBJECTIVE: To examine the hemodynamic patterns of critically ill patients with septicemia to evaluate their relationship to blood bacteriology. DESIGN: Retrospective study. SETTING: Medical ICUs of a tertiary care medical center. PATIENTS: Total of 59 critically ill patients with bacteremia: 33 with Gram-positive and 26 with Gram-negative bacteremia. MEASUREMENTS: Hemodynamic variables and mixed venous oxygen saturation (SvO2) measurements associated with the highest cardiac index measured within 72 hrs of positive blood cultures. MAIN RESULTS: No significant differences in cardiac index, mean arterial pressure, systemic vascular resistance, oxygen extraction ratio, or SvO2 were observed comparing the two groups. CONCLUSION: We were unable to demonstrate clinically important differences between the hemodynamic responses to Gram-positive vs. Gram-negative sepsis.

Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. The Ibuprofen Study Group.

OBJECTIVE: To evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Three university hospital medical ICUs. PATIENTS: Twenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter. INTERVENTIONS: Thirteen patients received placebo and 16 received ibuprofen that consisted of 600 mg (n = 11) or 800 mg (n = 5) iv over 20 mins, followed by three 800-mg doses administered as a rectal solution every 6 hrs. The initial iv dose was given within 4 hrs of the presumptive diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: The peak circulating total ibuprofen concentration after the iv dose (49.4 +/- 4.5 micrograms/mL, mean +/- SEM) was higher than peak concentrations after the three rectal doses (17.0 +/- 2.7, 16.4 +/- 3.0, 16.0 +/- 3.1 micrograms/mL). Both routes of ibuprofen administration were well tolerated. Frequent monitoring for gastrointestinal bleeding and assessment of renal and hepatic function failed to demonstrate significant differences between ibuprofen and placebo. Because a trend for reduced creatinine clearance was observed at 8 hrs in the ibuprofen group, nephrotoxicity of this drug in sepsis cannot be excluded. Temperature decreased significantly within 4 hrs of the initial dose of investigational therapy in patients who received ibuprofen (38.5 +/- 0.3 degrees to 37.0 +/- 0.2 degrees C, p less than .001). However, despite this significant change in temperature, we were unable to detect significant differences in hemodynamic and respiratory values or survival when ibuprofen-treated patients were compared with controls. CONCLUSIONS: Ibuprofen was well tolerated when administered iv and rectally to patients with severe sepsis, although drug absorption was poor with the rectal route. Significant antipyretic effects of ibuprofen were demonstrated. Although an excellent safety profile characterized ibuprofen in this study, the absence of ibuprofen-associated toxicity may have been secondary to poor rectal absorption of the drug. Our results support the continued clinical investigation of ibuprofen in sepsis, using an all-intravenous route of administration.

Lactate levels as predictors of the relationship between oxygen delivery and consumption in ARDS.

We reviewed the changes in Do2 and Vo2 in 58 patients with ARDS after interventions which included fluid loading, blood transfusion, and PEEP. After a significant change in Do2, patients with lactic acidosis (lactate level greater than 2.4 mmol/L) exhibited significant corresponding changes in Vo2 (p less than 0.001); however, no change in Vo2 was observed in patients without lactic acidosis (1-beta greater than 0.8). We conclude that a biphasic pattern of oxygen utilization in patients with ARDS emerges when subsets of patients with and without lactic acidosis are compared. Lactic acidosis, a marker of anaerobic metabolism, may be a characteristic of patients with ARDS who exhibit changes in Vo2 that are dependent on changes in Do2.

The use of crystalloidal and colloidal solutions for volume replacement in hypovolemic shock.

A wide variety of colloidal and crystalloidal fluids, as well as blood and blood products, are available to the clinician for treatment of the hypovolemic patient. These fluids vary with respect to the size, shape, and concentrations of electrolytes, colloidal molecules, and/or cellular components, duration of volume-expanding effects, incidence of allergic reactions, and effect on the coagulation system. When these fluids are administered intravenously, their distribution in the vascular, interstitial, and cellular compartments can be predicted from fundamental physiological principles as well as from the results of laboratory and clinical research. It is thus recognized that colloidal fluids and blood provide more rapid expansion of the intravascular space when compared with crystalloidal fluids. Similar volumes of crystalloidal fluids more rapidly expand the interstitial and intracellular spaces. These principles guide therapy in hypovolemic shock. A logical decision regarding intravenous fluid therapy may be based on the nature of the volume deficit (blood, plasma, or selective protein loss, loss of free water and/or electrolytes) and the predicted changes in cellular and extracellular compartments.