James B. Haenel

Postinjury multiple organ failure: a bimodal phenomenon

To better define the epidemiology of postinjury multiple organ failure (MOF), we prospectively evaluated 457 high-risk trauma patients who survived more than 48 hours. Overall, 70 (15%) developed MOF. In 27 (39%) patients, the occurrence was early, while in 43 (61%) patients the presentation was delayed. At presentation, early MOF had more cardiac dysfunction, while late MOF had greater hepatic failure. Indices of shock were more critical risk factors for early MOF, while advanced age was more important for late MOF. While early and late MOF had a similar high incidence of major infections, these appeared to be more important in precipitating late MOF. Finally, while mortality is similar, early MOF patients appear to succumb faster. In conclusion, postinjury MOF remains a significant challenge and appears to present in at least two patterns (i.e., early versus late). Better understanding of the relative roles of the dysfunctional inflammation and infections in early MOF versus late MOF may facilitate the development of new strategies for the prevention and treatment of morbid syndrome.

Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer?

BACKGROUND Recent military experience suggests that immediate 1:1 fresh frozen plasma (FFP); red blood cells (RBC) for casualties requiring >10 units packed red blood cells (RBC) per 24 hours reduces mortality, but no clinical trials exist to address this issue. Consequently, we reviewed our massive transfusion practices during a 5-year period to test the hypothesis that 1:1 FFP:RBC within the first 6 hours reduces life threatening coagulopathy. METHODS We queried our level I trauma centers prospective registry from 2001 to 2006 for patients undergoing massive transfusion. Logistic regression was used to evaluate the independent effect of FFP:RBC in 133 patients who received >10 units RBC in 6 hours on (1) Coagulopathy (international normalized ratio [INR] >1.5 at 6 hours), controlling for our previously described risk factors predictive of coagulopathy, as well as RBC, FFP, and platelet administration (2) Death (controlling for all variables plus age, crystalloids per 24 hours, INR >1.5 at 6 hours). RESULTS Overall mortality was 56%; 50% died from acute blood loss in the operating room. Over 80% of the RBC transfusions were completed in the first 6 hours: (Median RBC: 18 units) Median FFP:RBC survivors, 1:2, nonsurvivors: 1:4. (p < 0.001) INR >1.5 at 6 hours occurred in 30 (23%); 81% died. Regarding mortality, logistic regression showed significant variables (p < 0.05) included: RBC per 6 hours (OR = 1.248, 95%CI: 1.957-53.255), INR at 6 hours >1.5 (OR = 10.208, 95% CI: 1.957-53.255), ED temperature <34 degrees C (OR = 15.491, 95% CI 1.376-174.396), and age >55 years (OR = 40.531, CI 5.315-309.077). The adjusted OR for FFP:RBC ratio including the quadratic term was found to follow a U-shaped association (quadratic term estimate 0.6737 +/- 0.0345, p = 0.0189). CONCLUSION Although our data suggest that 1:1 FFP:RBC reduced coagulopathy, this did not translate into a survival benefit. Our findings indicate that the relationship between coagulopathy and mortality is more complex, and further clinical investigation is necessary before recommending routine 1:1 in the exsanguinating trauma patient.

Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome.

OBJECTIVE The expression of proinflammatory cytokines is rapidly increased in experimental models of the acute respiratory distress syndrome (ARDS), in patients at risk for ARDS, and in patients with established ARDS. Because multiple cytokines are present in bronchoalveolar lavage fluid, a common, proximal activation mechanism may operate in these settings. The proinflammatory cytokines whose expression is increased in the lungs of patients with ARDS have binding sequences in their enhancer/promoter regions for transcriptional regulatory proteins, such as nuclear factor-kappa B (NF-kappa B), nuclear factor-IL6 (NF-IL6), cyclic adenosine monophosphate responsive element binding protein, serum protein-1, and activating protein-1. To test the hypothesis that activation of one or more of these nuclear transcriptional regulatory factors might provide a common mechanism for the simultaneous expression of multiple cytokine genes in the setting of ARDS, we measured activation of these factors in alveolar macrophages from patients with ARDS and from controls. DESIGN Prospective, clinical study. SETTING Medical and surgical intensive care units at a university hospital and a county hospital. PATIENTS Twelve patients, six with established ARDS and six control patients without lung injury. INTERVENTIONS Patients with ARDS and controls underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated from lavage fluid and the nuclear proteins were extracted. Activation of transcriptional factors NF-kappa B, NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, and serum protein-1 was determined using an electrophoretic mobility shift assay, followed by densitometry of the autoradiographed gels. MEASUREMENTS AND MAIN RESULTS There were no significant differences in gender, age, tobacco smoking, Acute Physiology and Chronic Health Evaluation II score, quantity of lavage fluid, or number of alveolar macrophages in lavage specimens in the patient groups. Acute Lung Injury score and the Pao2/Fio2 ratio differed significantly between controls and ARDS patients: 0.46 +/- 0.17 vs. 2.74 +/- 0.14 (p < .0001) and 310 +/- 45 torr (41.3 +/- 6.0 kPa) vs. 150 +/- 11 torr (21.3 +/- 1.5 kPa) (p < .006), respectively. The mean Fio2 of the control patients was not significantly different from the mean Fio2 of ARDS patients: 0.47 +/- 0.11 vs. 0.55 +/- 0.6 (p = .53). Patients with ARDS had significantly (p < .02) increased activation of NF-kappa B in alveolar macrophages compared with patients without the syndrome. There was no evidence of increased activation of the transcriptional factors activating protein-1, serum protein-1, NF-IL6, or cyclic adenosine monophosphate responsive element binding protein in alveolar macrophages from ARDS vs. control patients. CONCLUSIONS These experiments demonstrated increased in vivo activation of the nuclear transcriptional regulatory factor NF-kappa B (but not NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, or serum protein-1) in alveolar macrophages from patients with ARDS. Because binding sequences for NF-kappa B are present in the enhancer/promoter sequences of multiple proinflammatory cytokines, activation of NF-kappa B may contribute to the increased expression of multiple cytokines in the lung in the setting of established ARDS.

Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multiple organ failure.

Untreated flow-dependent oxygen consumption (VO2) has recently been implicated as an unrecognized risk factor for multiple organ failure (MOF). We therefore prospectively studied 39 severely injured patients with known risk factors for multiple organ failure who were subjected to an established resuscitation protocol aimed at maximizing oxygen delivery (DO2 greater than 600 mL/min.m2) to attain a VO2 goal of greater than 150 mL/min.m2. Fifteen (38%) of these high risk patients did not meet this VO2 goal by 12 hours. These nonresponding patients had significantly elevated lactate levels, suggesting defective aerobic metabolism. Of note, this blunted VO2 response despite maximal efforts to enhance peripheral oxygen availability predicted MOF. These data serve to re-emphasize the importance of the initial shock insult in causing or priming the host for the development of late MOF.

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery.

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.

Diagnosing pneumonia in mechanically ventilated trauma patients: endotracheal aspirate versus bronchoalveolar lavage.

We prospectively investigated the diagnostic value of semiquantitative (semiQC) and quantitative (QC) cultures of endotracheal aspirate (ETA) compared with QC of bronchoalveolar lavage (BAL) fluids in 18 mechanically ventilated trauma patients with clinical signs of pneumonia. The general agreement between QC of ETA and BAL was 89% when conventional cutoffs for the QC were used and 94% if the cutoffs were adjusted for previous antibiotic therapy. In all six patients whose clinical diagnoses of pneumonia were considered definite, both QC of ETA and QC of BAL were positive; however, standard semiQC of ETA showed comparable results in this group. On the contrary, in the 12 patients whose clinical diagnoses were uncertain, QC of BAL and ETA were negative in ten patients and in five (50%) of these, pneumonia was eventually excluded. Semiquantitative cultures of ETA were positive in all these patients. Five (28%) patients experienced a decrease in PaO2/FiO2 (> 15% of previous value) 2 hours after BAL, and in three (17%) this derangement persisted for 24 hours. These data suggest that BAL may be hazardous in mechanically ventilated trauma patients and that its use should be restricted to patients in whom the diagnosis is in doubt.

Post-traumatic pulmonary pseudocyst in the adult: pathophysiology, recognition, and selective management

Pulmonary contusion is the usual manifestation of lung parenchymal injury following blunt chest trauma. With rapid deceleration, however, parenchymal lacerations can result in cavities best termed post-traumatic pulmonary pseudocyst (PPP). This report discusses eight adult PPP cases encountered at the Denver General Hospital over the past 30 months. Five were males and the mean age was 29 years (range, 18 to 54). Injury mechanism was motor vehicle accident in four, industrial machinery in two, autopedestrian accident in one, and large-animal rodeo rollover in another. Review of daily portable anteroposterior chest roentgenograms revealed parenchymal infiltrates consistent with pulmonary contusion that typically cavitated within the first week. Computed tomography of the chest was pursued in complicated patients and clearly influenced therapy. Three (38%) pseudocysts developed into lung abscesses; two required resection and the other responded to percutaneous drainage. Although previously described as a benign pediatric entity, in our adult experience, PPP may result in a recalcitrant lung abscess requiring aggressive intervention.

Cardiopulmonary effects of permissive hypercapnia in the management of adult respiratory distress syndrome

BACKGROUND Despite numerous advances, the mortality from adult respiratory distress syndrome (ARDS) remains high. Traditional ventilator management in ARDS has been to maintain normal PaCO2 by positive pressure ventilation (PPV). However, high levels of PPV may worsen the lung injury by alveolar overdistension. Permissive hypercapnia (PHC) has been proposed as an alternative method of ventilation, but hypercapnia may affect the hemodynamics of a hyperdynamic, critically ill patient. The purpose of this study was to determine the effect of PHC on ventilator requirement, arterial oxygenation, and hemodynamic performance in patients with severe ARDS. METHODS Ten men and 5 women with established ARDS (mean Murray lung injury score 3.42 +/- 0.1) were prospectively studied using an established protocol when the static pulmonary plateau pressure (Pplat) exceeded 40 cm H2O. The initial tidal volume (V(t)) was decreased to achieve a Pplat < 40 cm H2O or to a lower limit of 5 cc/kg. Arterial blood gas and hemodynamic data were obtained serially. RESULTS The V(t) was reduced from 9.9 +/- 0.5 mL/kg to 7.7 +/- 0.5 mL/kg at 24 hours, p < 0.05. This reduction of V(t) produced a decrease in minute ventilation (Ve: 18.0 +/- 1.6 to 11.9 +/- 0.7 L/min, p < 0.05), peak airway pressure (PAP: 55 +/- 2 vs 45 +/- 3 cm H2O, p < 0.05), and Pplat (Pplat 45.4 +/- 1.5 vs. 36.7 +/- 1.9) at 24 hours. The PaCO2 rose from 37.9 +/- 1.3 to 56.7 +/- 3.0 mm Hg (p < 0.05), and the pH decreased from 7.41 +/- 0 to 7.31 +/- 0 (p < 0.05) at 24 hours. There were no significant changes in mean airway pressure, static compliance, arterial oxygenation, pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption. CONCLUSIONS Permissive hypercapnia by V(t) reduction: (1) decreased Ve, PAP, and Pplat without a change in mean airway pressure, static compliance or arterial oxygenation; (2) caused a mild partially compensated acidosis; and (3) does not adversely affect pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption.

Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome.

INTRODUCTION Prone ventilation improves oxygenation in selected patients with acute respiratory distress syndrome (ARDS). However, prone positioning of critically ill patients with multiple invasive lines and tubes is potentially dangerous. Trauma patients, in particular, may require special consideration because of skeletal fixation devices or prior operative procedures. Our objective was to critically evaluate our experience with prone positioning in patients with severe postinjury ARDS. METHODS Injured patients admitted to our Level I trauma center who developed ARDS were prospectively identified. Serial lung injury severity and pulmonary mechanical data, as well as complications of prone ventilation were recorded. RESULTS During the 12-month period ending August of 1998, nine patients with postinjury ARDS were treated with prone ventilation because of hypoxemia refractory to other ventilatory strategies. All patients suffered blunt trauma. Their mean age was 29 +/- 4.5 years; seven patients were men. The average Injury Severity Score was 26 +/- 5; and, at the time of prone positioning, the mean Lung Injury Score was 3.5. The mean PaO2/FIO2 ratio increased from 75 +/- 7 to 147 +/- 27 with prone ventilation (p < 0.05, paired t test); and in six patients, the FIO2 could be decreased. Four major complications occurred (44%). One patient experienced a midline abdominal wound dehiscence. Severe facial or upper chest wall pressure necrosis developed in two patients, despite extensive padding and careful attention to skin care. The fourth patient sustained a cardiac arrest immediately after prone positioning. CONCLUSION Prone ventilation in postinjury patients with ARDS may improve oxygenation but has the potential for significant complications. Careful consideration is required before prone positioning in this subset of patients.

Pneumonia: Cause or symptom of postinjury multiple organ failure?

Recent studies have shown that selective gut decontamination can reduce the incidence of pneumonia, but this does not decrease multiple organ failure (MOF) or mortality. These findings have prompted the hypothesis that pneumonia is an inconsequential symptom of MOF. To test this, we prospectively evaluated 123 high-risk trauma patients (mean Injury Severity Score = 36.2 +/- 1.5). Organ dysfunction, scored daily according to a 12-point scale, ultimately developed in 28 (23%) patients. Major infections were diagnosed, based on strict criteria, in 59 patients (48%), and pneumonia developed in 52 patients (43%). Pneumonia was significantly associated with MOF (82% of patients with MOF versus 30% of patients without MOF, p < 0.0001). In 14 (50%) of the patients with MOF, pneumonia preceded a significant rise (greater than or equal to 3) in serial MOF scoring. Of note, 10 (71%) of these patients died. Among the remaining 14 patients with MOF, 10 developed pneumonia, but this was associated with a minimal increase (less than or equal to 2) in MOF scoring (3 patients died). These data, by temporal association with MOF scoring, implicate pneumonia in precipitating or significantly worsening organ failure in 50% of the patients who developed MOF.