Jay L. Falk

Lactic acidosis in critical illness.

PurposeThis article reviews the current body of knowledge regarding lactic acidosis in critically ill patients. The classification of disordered lactate metabolism and its pathogenesis are examined. The utility of lactate as a metabolic monitor of shock is examined and current therapeutic strategies in the treatment of patients suffering from lactic acidosis are extensively reviewed. The paper is designed to integrate basic concepts with a current approach to lactate in critical illness that the clinician can use at the bedside. Data SourcesComprehensive review of the available, basic science, medical, surgical, and critical care literature. ConclusionsThe severity of lactic acidosis in critically ill patients correlates with overall oxygen debt and survival. Lactate determinations may be useful as an ongoing monitor of perfusion as resuscitation proceeds. Therapy of critically ill patients with lactic acidosis is designed to maximize oxygen delivery in order to reduce tissue hypoxia by increasing cardiac index, while maintaining hemoglobin concentration. Buffering agents have not been shown to materially affect outcome from lactic acidosis caused by shock. The benefits of other specific therapies designed to reduce the severity of lactic acidosis remain unproven. (Crit Care Med 1992; 20:80)

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.

End-tidal carbon dioxide concentration during cardiopulmonary resuscitation.

We prospectively measured the end-tidal carbon dioxide concentration during 13 episodes of cardiac arrest in 10 critically ill patients receiving mechanical ventilation, to evaluate its usefulness as an indicator of circulatory status during cardiac arrest and resuscitation. The end-tidal carbon dioxide concentration decreased from a mean (+/- SD) of 1.4 +/- 0.9 to 0.4 +/- 0.4 percent after the onset of cardiac arrest. During precordial compression, it increased to 1.0 +/- 0.5 percent. The decreases in the end-tidal carbon dioxide concentration were associated with increases in systemic oxygen extraction (r = 0.79). Spontaneous circulation was restored on seven occasions. This was heralded by a rapid increase in the end-tidal carbon dioxide concentration, from 1.3 +/- 0.5 percent to an overshoot value of 3.7 +/- 2.1 percent, within approximately 30 seconds. The concentration then declined to a stable value of 2.4 +/- 1.8 percent four minutes after resuscitation. However, it remained 0.7 +/- 0.4 percent in six patients in whom resuscitative efforts failed to restore spontaneous circulation. These observations are consistent with experimental studies of cardiopulmonary resuscitation in pigs, in which the end-tidal carbon dioxide concentration varied directly with the cardiac output produced by precordial compression. We therefore propose that measurement of the end-tidal carbon dioxide concentration may be a practical, non-invasive method for monitoring blood flow generated by precordial compression during cardiopulmonary resuscitation and an almost immediate indicator of successful resuscitation.

Oxygen delivery and consumption in patients with hyperdynamic septic shock.

We analyzed the relationship of increases in oxygen delivery to changes in oxygen consumption in ten patients with hyperdynamic septic shock. Increases in oxygen delivery from 413 ± 14 (SEM) to 535 ± 19 ml/min-m2 (p < .01) were associated with increases in oxygen consumption from 136 ± 10 to 161 ± 5 ml/min-m2 (p < .05). Arterial lactate decreased from 4.6 ± 1.6 to 2.1 ± 0.3 mmol/L (p < .05). These observations suggest that oxygen utilization is perfusion-limited in hyperdynamic septic shock.

Elevated Levels of Serum Glial Fibrillary Acidic Protein Breakdown Products in Mild and Moderate Traumatic Brain Injury Are Associated With Intracranial Lesions and Neurosurgical Intervention

STUDY OBJECTIVE This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.

BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL ± standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13–15 and 10 with GCS score 9–12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82–0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81–0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (±0.254) and 1.618 (±0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62–0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76–0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. LEVEL OF EVIDENCE: II, prognostic study.

Relationship of oxygen delivery and mixed venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction

Critical decreases in oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2) are associated with anaerobic metabolism and, therefore, lactic acidosis. We studied 50 consecutive patients with sepsis and 50 consecutive patients with acute myocardial infarction (AMI) in whom the arterial blood lactate was greater than 1 mmol/L in order to determine critical thresholds of DO2 and SvO2. In both groups, critical values of DO2 or SvO2 associated with lactic acidosis could not be identified. The DO2 ranged from 136 to 811 ml/min.m2 and SvO2 ranged from 28% to 73% in the patients with sepsis. The DO2 ranged from 115 to 434 ml/min.m2 and SvO2 from 17% to 72% in patients with AMI. The absence of threshold values for DO2 and SvO2 probably reflects the influence of distributive flow abnormalities as well as differences in metabolic requirements in these critically ill patients.

Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion.

Twenty consecutive patients with severe sepsis were randomized to fluid challenge with 5% albumin or 10% low MW hydroxyethyl starch (pentastarch) solutions. Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure (WP) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused. Hemodynamic, respiratory, and coagulation profiles were measured before and after fluid infusion. The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups. Both colloid infusions resulted in similar increases in cardiac output, stroke output, and stroke work. The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin, although pentastarch was associated with a 45% decrease in factor VIII:c. We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis.

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.

Effect of ventilation on acid-base balance and oxygenation in low blood-flow states.

Objectives: To investigate how minute ventilation affects the partial pressure of end‐tidal CO2 and arterial and mixed venous pH, Pco2, Po2, and the concentration of bicarbonate during low blood‐flow states. We tested the null hypothesis that acid‐base conditions during low rates of blood flow are not significantly different when minute ventilation is doubled or halved. Design: Prospective, experimental, animal study. Setting: University hospital laboratory. Subjects: Domestic swine. Interventions: We studied ten anesthetized and mechanically ventilated swine (weight, 43 to 102 kg) in a new model of controlled systemic and pulmonary blood flow in which each animal was maintained on ventricular assist devices. After electrical induction of ventricular fibrillation, ventricular assist device blood flow was decreased in steps. At each decrease, control minute ventilation, two times the control minute ventilation (hyperventilation), and onehalf the control minute ventilation (hypoventilation) were administered; each ventilatory change was maintained for 6 mins. Measurements and Main Results: Aortic, pulmonary arterial and central venous pressures, ventricular assist device blood flow, and endtidal CO2 were recorded continuously. Acid‐base conditions were studied at three different mean blood flow rates: 49%, 30%, and 12% of baseline prearrest cardiac index. Arterial pH and Pao2 and mixed venous pH varied directly ( p < .003) with minute ventilation, while Paco2 and mixed venous Pco2, and end‐tidal CO2 varied inversely ( p < .0001) with minute ventilation. Mixed venous Po2 was not significantly related to minute ventilation ( p = .6). Paco2 and arterial bicarbonate; mixed venous pH, mixed venous Po2, and mixed venous bicarbonate, and end‐tidal CO2 varied directly (p < .001) with blood flow, while mixed venous Pco2 varied inversely with blood flow (p < .05). Arterial pH was not significantly related to blood flow ( p = .3). When minute ventilation changed from hyperventilation to hypoventilation at a mean blood flow rate of 49%, mean arterial pH decreased 0.22 ± 0.06 (p < .05), mean Paco2 increased 28 ± 6 torr (3.7 ± 0.8 kPa) (p < .05), and mean Pao2 decreased 99 ± 77 torr (13.2 ± 10 kPa); mean mixed venous pH decreased 0.11 ± 0.02, mean mixed venous Pco2 increased 16 ± 2.2 torr (2.1 ± 0.3 kPa) (p < .05), and mean mixed venous Po2 did not change; mean endtidal CO2 increased 18 ± 2 torr (2.4 ± 0.3 kPa) ( p < .05). The effect of changes in minute ventilation on blood gases and end‐tidal CO2 was similar for mean blood flow rates of 30% and 12% of baseline cardiac index. Conclusions: During low rates of blood flow similar to those rates found in shock and cardiopulmonary resuscitation, alterations in minute ventilation significantly influenced end‐tidal CO2 and both arterial and mixed venous pH and Pco2. These findings may have clinical importance in improving the treatment of shock and cardiac arrest. (Crit Care Med 1994; 22:1827–1834)