Marilyn T. Haupt

Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock.

Twenty-six consecutive patients in hypovolemic shock were randomized to fluid challenge with 5% albumin (A), 6% hetastarch (H), or 0.9% saline (S) solutions. Fluid challenge consisted of 250 ml of test fluid every 15 min until the pulmonary artery wedge pressure (WP) reached 15 mm Hg. Thereafter, WP was maintained at 15 mm Hg for an additional 24 h with infusions of the same test fluid. Vital signs, hemodynamic and respiratory variables, as well as arterial lactate and colloid osmotic pressure (COP) were monitored according to protocol. Chest x-rays were performed by standardized technique before fluid challenge and at 12 and 24 h of maintenance fluid therapy and were evaluated for evidence of pulmonary edema. Cardiac function and hemodynamic stability were restored by fluid challenge with A, H, and S. Two to 4 times the volume of S as A or H was required to achieve similar hemodynamic endpoints. COP was increased by fluid challenge with A or H but was markedly reduced by fluid challenge with S and throughout the 24-h maintenance period. Fluid challenge resulted in reductions in COP-WP gradient of 62% in the A, 43% in the H, and 125% in the S groups. Resuscitation with S resulted in a significantly higher incidence of pulmonary edema (87.5%) than did resuscitation with A (22%) or H (22%). Urine output was not different among the groups at any time during the study. We conclude that 6% H performs as well as 5% A as a resuscitative fluid and that resuscitation with either of these colloids is associated with a lower incidence of pulmonary edema than is resuscitation with 0.9% S.

Guidelines on critical care services and personnel: Recommendations based on a system of categorization of three levels of care.

ObjectivesTo describe three levels of hospital-based critical care centers to optimally match services and personnel with community needs, and to recommend essential intensive care unit services and personnel for each critical care level. ParticipantsA multidisciplinary writing panel of professionals with expertise in the clinical practice of critical care medicine working under the direction of the American College of Critical Care Medicine (ACCM). Data Sources and SynthesisRelevant medical literature was accessed through a systematic Medline search and synthesized by the ACCM writing panel, a multidisciplinary group of critical care experts. Consensus for the final written document was reached through collaboration in meetings and through electronic communication modalities. Literature cited included previously written guidelines from the ACCM, published expert opinion and statements from official organizations, published review articles, and nonrandomized, historical cohort investigations. With this background, the ACCM writing panel described a three-tiered system of intensive care units determined by service-based criteria. ConclusionsGuidelines for optimal intensive care unit services and personnel for hospitals with varying resources will facilitate both local and regional delivery of consistent and excellent care to critically ill patients.

Effect of ibuprofen in patients with severe sepsis : a randomized, double-blind, multicenter study

ObjectiveTo evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis. DesignRandomized, double-blind, placebo-controlled trial. SettingThree university hospital medical ICUs. PatientsTwenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter. InterventionsThirteen 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 ResultsThe peak circulating total ibuprofen concentration after the iv dose (49.4 ± 4.5 μg/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 μg/ 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° to 37.0 ± 0.2°C, p < .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. ConclusionsIbuprofen 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.

Colloid osmotic pressure and fluid resuscitation with hetastarch, albumin, and saline solutions.

The effects of fluid resuscitation with 6% hetastarch, 5% albumin, or 0.9% saline solutions on plasma colloid osmotic pressure (COP) were examined in 26 patients with hypovolemic circulatory shock. One liter of hetastarch produced a 36% increase in COP compared to an 11% increase after 1 L of albumin (p < 0.001). One liter of saline resulted in a 12% decrease in COP (p < 0.05). The mean COP increased from 16.3 ± 1.6 (SE) mm Hg to a maximum of 23.7 ±1.4 mm Hg during the first 24 h of hetastarch resuscitation (p < 0.01), and from 17.0 ± 1.1 to 22.3 ± 1.5 mm Hg with albumin (p < 0.001). Saline resuscitation decreased the COP from 17.1 ± 1.1 mm Hg to a minimum of 12.7 ± 1.1 mm Hg (p < 0.02). These changes persisted from 2–5 days after resuscitation. Saline resuscitation required significantly larger amounts of fluid. The authors conclude that fluid resuscitation of circulatory shock with colloid solutions increases COP and requires less volume of resuscitative fluid.

Guidelines for critical care medicine training and continuing medical education.

ObjectiveCritical care medicine trainees and faculty must acquire and maintain the skills necessary to provide state-of-the art clinical care to critically ill patients, to improve patient outcomes, optimize intensive care unit utilization, and continue to advance the theory and practice of critical care medicine. This should be accomplished in an environment dedicated to compassionate and ethical care. ParticipantsA multidisciplinary panel of professionals with expertise in critical care education and the practice of critical care medicine under the direction of the American College of Critical Care Medicine. ScopePhysician education in critical care medicine in the United States should encompass all disciplines that provide care in the intensive care unit and all levels of training: from medical students through all levels of postgraduate training and continuing medical education for all providers of clinical critical care. The scope of this guideline includes physician education in the United States from residency through ongoing practice after subspecialization. Data Sources and SynthesisRelevant literature was accessed via a systematic Medline search as well as by requesting references from all panel members. Subsequently, the bibliographies of obtained literature were reviewed for additional references. In addition, a search of organization-based published material was conducted via the Internet. This included but was not limited to material published by the American College of Critical Care Medicine, Accreditation Council for Graduate Medical Education, Accreditation Council for Continuing Medical Education, and other primary and specialty organizations. Collaboratively and iteratively, the task force met, by conference call and in person, to construct the tenets and ultimately the substance of this guideline. ConclusionsGuidelines for the continuum of education in critical care medicine from residency through specialty training and ongoing throughout practice will facilitate standardization of physician education in critical care medicine.

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

ObjectiveTo examine the hemodynamic patterns of critically ill patients with septicemia to evaluate their relationship to blood bacteriology. DesignRetrospective study. SettingMedical ICUs of a tertiary care medical center. PatientsTotal of 59 critically ill patients with bacteremia: 33 with Gram-positive and 26 with Gram-negative bacteremia. MeasurementsHemodynamic variables and mixed venous oxygen saturation (SMo2) measurements associated with the highest cardiac index measured within 72 hrs of positive blood cultures. Main ResultsNo significant differences in cardiac index, mean arterial pressure, systemic vascular resistance, oxygen extraction ratio, or SMo2 were observed comparing the two groups. ConclusionWe were unable to demonstrate clinically important differences between the hemodynamic responses to Gram-positive vs. Gram-negative sepsis.

Implementation of Clinical Practice Guidelines for Ventilator-associated Pneumonia: A Multicenter Prospective Study*

Objective:Ventilator-associated pneumonia is an important cause of morbidity and mortality in critically ill patients. Evidence-based clinical practice guidelines for the prevention, diagnosis, and treatment of ventilator-associated pneumonia may improve outcomes, but optimal methods to ensure implementation of guidelines in the intensive care unit are unclear. Hence, we determined the effect of educational sessions augmented with reminders, and led by local opinion leaders, as strategies to implement evidence-based ventilator-associated pneumonia guidelines on guideline concordance and ventilator-associated pneumonia rates. Design:Two-year prospective, multicenter, time-series study conducted between June 2007 and December 2009. Setting:Eleven ICUs (ten in Canada, one in the United States); five academic and six community ICUs. Patients:At each site, 30 adult patients mechanically ventilated >48 hrs were enrolled during four data collection periods (baseline, 6, 15, and 24 months). Intervention:Guideline recommendations for the prevention, diagnosis, and treatment of ventilator-associated pneumonia were implemented using a multifaceted intervention (education, reminders, local opinion leaders, and implementation teams) directed toward the entire multidisciplinary ICU team. Clinician exposure to the intervention was assessed at 6, 15, and 24 months after the introduction of this intervention. Measurements and Main Results:The main outcome measure was aggregate concordance with the 14 ventilator-associated pneumonia guideline recommendations. One thousand three hundred twenty patients were enrolled (330 in each study period). Clinician exposure to the multifaceted intervention was high and increased during the study: 86.7%, 93.3%, 95.8%, (p < .001), as did aggregate concordance (mean [SD]): 50.7% (6.1), 54.4% (7.1), 56.2% (5.9), 58.7% (6.7) (p = .007). Over the study period, ventilator-associated pneumonia rates decreased (events/330 patients): 47 (14.2%), 34 (10.3%), 38 (11.5%), 29 (8.8%) (p = .03). Conclusions:A 2-yr multifaceted intervention to enhance ventilator-associated pneumonia guideline uptake was associated with a significant increase in guideline concordance and a reduction in ventilator-associated pneumonia rates.

Is it time to use blood volume measurements as a clinical tool

This months issue of Critical Care Medicine features a study by Dr. Thomas and colleagues (1) in which blood volume is measured using a minimally invasive technique that uses fluorescent-labeled hydroxyethyl starch. In this study, the intravenous injection of this marker into patients was followed by three sequential samplings of blood during the next 20-30 mins. The fluorescence of each sample was measured spectrometrically and blood volume was calculated. Using radiolabeled red cells as a criterion, the authors demonstrated a strong linear relationship between blood volume assessments by the two methods (slope = 0.97) although a constant bias (blood volume was greater with the hydroxyethyl starch method) was observed. The authors conclude that their method was a valid alternative to red cell labeling in the calculation of blood volume in patients.

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.

Does colloid resuscitation minimize lung edema

Ever since Starling (1) hypothesized that fluid flux across the capillary membrane was governed by a balance between oncotic and hydrostatic forces and influenced by permeability, clinicians have been seeking resuscitative fluids with oncotic properties to prevent or minimize the formation of edema. Using Starling’s model, benefits of colloids in the resuscitation of shock are likely to be more pronounced in nonpermeability than permeability shock because loss of colloid through permeable capillaries will reduce the retention of fluid in the intravascular space. There is considerable interest in the effects of colloids on edema formation in the lung because of the role of this organ in gas exchange and oxygen delivery. Colloids have been popular fluids for resuscitation for all types of shock because of these theoretical benefits. Colloids that are commercially available today for patient use include 5% albumin, 4% gelatin (available in Europe), and 6% hydroxyethyl starch. Each of these colloids has oncotic properties that approximate those of human plasma. They have been studied in a large number of clinical trials of critically ill patients with and without permeability disorders and compared with conventional crystalloid fluids. The results of these studies have been conflicting and often controversial. One of the problems with early studies comparing colloids and crystalloids is that experimental resuscitation protocols did not always mimic the approach used by the bedside clinician. Many studies compared arbitrary aliquots of colloid with larger aliquots of crystalloid because of the tendency of crystalloid to move from the circulating space to the interstitial space. There was difficulty in extrapolating these results to the bedside because clinicians rarely use a predetermined volume to resuscitate patients. In more recent times, comparative colloid/crystalloid studies have used protocols that resuscitate to physiologic end points. These end points, which may include blood pressure, urine output, central venous pressure, and/or pulmonary artery occlusion pressure reflect current approaches to the management of shock in critically ill patients. The study reported in this issue of Critical Care Medicine by van der Heijden et al (2) attempts to compare colloid with crystalloid resuscitation using physiologic guides to fluid resuscitation. They compared the two types of resuscitative fluids in groups of patients with and without sepsis, a common permeability disorder. They examined the effects of fluid resuscitation on the lung. After resuscitation, they measured a pulmonary leak index with Gallium-67–labeled transferrin, extravascular lung water using a thermal dye dilution technique, and a lung injury score using a standardized chest radiograph interpretation method. They compared the crystalloid 0.9% NaCl (normal saline) with colloid groups (4% gelatin, 6% hydroxyethyl starch, and 5% albumin). Because there was insufficient statistical power for comparisons between the individual colloids, they compared the crystalloid group with the colloid groups combined. Fluids were given using central venous pressure as a guide according to a modification of an algorithm (3) that required active fluid resuscitation until signs that the limits of right heart compliance were reached (e.g., a central venous pressure increase 5 mm Hg after a 200-mL aliquot infusion). The authors found no differences in extravascular lung water, pulmonary leak index, and lung injury score between the crystalloid and colloid groups. This negative result applied to both septic and nonseptic patients. Of interest, however, is that authors did note a significant inverse correlation between colloid oncotic pressure (COP)-central venous pressure gradient and extravascular lung water for all patients after the 90-min period of fluid loading. The COP-central venous pressure gradient sums the opposing hydrostatic and oncotic forces of fluid in the microvascular space, and a high gradient favors intravascular fluid retention. A similar inverse correlation between COP-pulmonary artery wedge pressure gradients and radiographically determined pulmonary edema has been observed in an earlier study of critically ill patients (4). One must be concerned that variability within the colloid groups may have masked a positive result favoring increased lung water accumulation in the crystalloid group. Indeed, the three colloids are distinctly different from one another. Albumin is a small lancet-shaped protein, gelatin is characterized by long polypeptide chains, and hydroxylethyl starch is a highly branched molecule. The colloids also differ with respect to half-life, degradation in the circulation, and oncotic properties. The authors also confirmed colloids to be potent volume expanders, a finding that has been observed in many studies. After 90 minutes of resuscitation, colloids produced greater increases in central venous pressure, cardiac index, and intrathoracic blood volume compared with crystalloids. The ability of colloids to rapidly restore circulating blood volume was upheld in this study and supports the practice of using these fluids in the early stages of resuscitation. The impact of colloids on lung water accumulation remains uncertain. Nevertheless, the significant correlation between COP-central venous pressure gradient and extravascular lung water in this study suggests that active interest in potentially beneficial effects of these fluids should be maintained. Marilyn T. Haupt, MD, FCCM Pulmonary and Critical Care Geisinger Health System Danville, PA *See also p. 1275.