James Haenel

The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery

BACKGROUNDnHuman polymerized hemoglobin (PolyHeme) is a universally compatible, disease-free, oxygen-carrying resuscitative fluid. This is the first prospective, randomized trial to compare directly the therapeutic benefit of PolyHeme with that of allogeneic red blood cells (RBCs) in the treatment of acute blood loss.nnnSTUDY DESIGNnForty-four trauma patients (33 male, 11 female) aged 19-75 years with an average Injury Severity Score (ISS) score of 21+/-10 were randomized to receive red cells (n = 23) or up to 6 U (300 g) of PolyHeme (n = 21) as their initial blood replacement after trauma and during emergent operations.nnnRESULTSnThere were no serious or unexpected adverse events related to PolyHeme. The PolyHeme infusion of 4.4+/-2.0 units (mean +/- SD) resulted in a plasma [Hb] of 3.9+/-1.3 g/dL, which accounted for 40% of the total circulating [Hb]. There was no difference in total [Hb] between the groups before infusion (10.4+/-2.3 g/dL control vs. 9.4+/-1.9 g/dL experimental). At end-infusion the experimental RBC [Hb] fell to 5.8+/-2.8 g/dL vs. 10.6+/-1.8 g/dL (p < 0.05) in the control, although the total [Hb] was not different between the groups or from pre-infusion. The total number of allogeneic red cell transfusions for the control and experimental groups was 10.4+/-4.2 units vs. 6.8+/-3.9 units (p < 0.05) through day 1, and 11.3+/-4.1 units vs. 7.8 +/-4.2 units (p = 0.06) through day 3.nnnCONCLUSIONSnPolyHeme is safe in acute blood loss, maintains total [Hb] in lieu of red cells despite the marked fall in RBC [Hb], and reduces the use of allogeneic blood. PolyHeme appears to be a clinically useful blood substitute.

Rapid thrombelastography (r-TEG) identifies hypercoagulability and predicts thromboembolic events in surgical patients.

BACKGROUNDnDespite routine prophylaxis, thromboembolic events (TEs) in surgical patients remain a substantial problem. Furthermore, the timing and incidence of hypercoagulability, which predisposes to these events is unknown, with institutional screening programs serving primarily to establish a diagnosis after an event has occurred. Emerging evidence suggests that point of care (POC) rapid thrombelastography (r-TEG) provides a real-time analysis of comprehensive thrombostatic function, which represents an analysis of both enzymatic and platelet components of thrombus formation. We hypothesized that r-TEG can be used as a screening tool to identify hypercoagulable states in surgical patients and would predict subsequent thromboembolic events.nnnMETHODSnRapid thrombelastography r-TEG analyses were performed on 152 critically ill patients in the surgical intensive care unit (ICU) during 7 months. Hypercoagulability was defined as clot strength (G)>12.4 dynes/cm(2). Variables of interest for identifying hypercoagulability and thromboembolic events included sex, age, operating hospital service, specific injury patterns, injury severity score (ISS), transfusion within first 24 h, ICU duration of stay, ventilator days, hospital admission days, and thromboprophylaxis. Comparisons between the hypercoagulable and normal groups or between the groups with and without thromboembolic events were performed using Chi-square tests or the Fisher exact test for categorical variables and independent sample t tests or Wilcoxon rank sum tests for continuous variables. Multivariate logistic regression analysis (LR) was performed to identify independent predictors of thromboembolic events. A receiver operating characteristic curve was used to measure the performance of G for predicting the occurrence of a TE event. All tests were 2-sided with significance of P < .05.nnnRESULTSnIn all, 86 patients (67%) were hypercoagulable by r-TEG. More than 85% of patients in the hypercoagulable group and 79% in the normal group received thromboprophylaxis during the study period. The differences between hypercoagulable and normal groups by bivariate analysis included high-risk injuries (52% vs 35%; P = .03), spinal cord injury (27% vs 12%; P = .03), median ICU duration of stay (13 vs 7 days; P < .001), median ventilator days (6 vs 2; P < .001), and median hospital duration of stay (20 vs 13 days; P < .001). A total of 16 patients (19%) of the hypercoagulable group suffered a thromboembolic event, and 10 hypercoagulable patients (12%) had thromboembolic events predicted by prior r-TEG hypercoagulability. No patients with normal coagulability by r-TEG had an event (P < .001). LR analysis showed that the strongest predictor of TE after controlling for the presence of thromboprophylaxis was elevated G value (odds ratio: 1.25, 95% confidence interval [CI]: 1.12-1.39). For every 1 dyne/cm(2) increase in G, the odds of a TE increased by 25%.nnnCONCLUSIONnThese results indicate that the presence of hypercoagulability identified by r-TEG is predictive of thromboembolic events in surgical patients. Subsequent study is necessary to define optimal prophylactic treatment strategies for patients with r-TEG proven hypercoagulability.

Evidence for early supply independent mitochondrial dysfunction in patients developing multiple organ failure after trauma.

OBJECTIVEnTo determine whether early supply independent mitochondrial oxidative dysfunction occurs in trauma patients who develop multiple organ failure (MOF).nnnDESIGNnProspective focused observational trial.nnnMETHODSnHigh-risk patients were aggressively resuscitated while being continuously monitored by near infrared spectroscopy. Near infrared spectroscopy monitoring strips allow for a direct comparison of changes in tissue oxyhemoglobin levels (HbO2), which reflect local oxygen supply, and cytochrome a,a3 redox, which reflects mitochondrial oxygen consumption. Under normal conditions, HbO2 and a,a3 redox are tightly coupled. On the other hand, decoupled HbO2 and a,a3 redox is a sign of mitochondrial oxidative dysfunction. Outcomes included MOF, oxygen delivery, oxygen consumption, lactate, and the presence of decoupled HbO2 and a,a3 redox.nnnRESULTSnTwenty-four high-risk patients were studied; nine (38%) developed MOF. At 12 hours of resuscitation, MOF and non-MOF patients did not have statistically different oxygen delivery and oxygen consumption, but lactate levels were significantly higher in MOF patients. Additionally, HBO2 and a,a3 redox were decoupled in eight (89%) MOF patients compared with two (13%) non-MOF patients (p < 0.05).nnnCONCLUSIONnSeverely injured trauma patients who develop MOF preferentially display evidence of mitochondrial oxidative dysfunction early in the course of their resuscitation despite early goal-oriented maximization of oxygen delivery.

One Thousand Bedside Percutaneous Tracheostomies in the Surgical Intensive Care Unit: Time to Change the Gold Standard

BACKGROUNDnBedside percutaneous tracheostomy (BPT) is a cost-effective alternative to open tracheostomy. Small series have consistently documented minimal morbidity, but BPT has yet to be embraced as the standard of care. Because this has been our preferred technique in the surgical ICU for more than 20 years, we reviewed our experience to ascertain its safety. We hypothesize that BPT has acceptably minimal morbidity, even in high-risk patients.nnnSTUDY DESIGNnPatients undergoing BPT from January 1998 to June 2008 were reviewed. High-risk patients were defined as those with cervical collar or halo, cervical spine injuries, systemic heparinization, positive end-expiratory pressure >10 cm H(2)O or fraction of inspired oxygen > 50%.nnnRESULTSnDuring the study period, 1,000 patients underwent BPT (74% men; mean ± SEM age 46 ± 0.6 years; 70% trauma). BPT was performed 8.9 ± 0.2 days (mean ± SEM) after admission. Patients remained ventilator dependent for an additional 9.7 ± 0.4 days (mean ± SEM). There were 482 (48%) patients undergoing BPT who were considered high-risk: 1 risk category, 273 patients; 2 risk categories, 139 patients; 3 risk categories, 56 patients; 4 risk categories, 12 patients; 5 risk categories, 2 patients. Complications occurred in 14 (1.4%) patients. Early complications included tracheostomy tube misplacement requiring revision (n = 4), bleeding requiring intervention (n = 2), infection (n = 1), and procedure failure requiring cricothyroidotomy (n = 1). Late complications included persistent stoma requiring operative closure (n = 4) and subglottic stenosis (n = 2). There were 6 complications (1.2%) in normal risk and 8 complications (1.7%) in high-risk patients. There were no deaths related to BPT.nnnCONCLUSIONSnBPT in the surgical intensive care unit is a safe procedure, even in high-risk patients. We believe BPT is the new gold standard for patients requiring tracheostomy for mechanical ventilation.

VENTILATORY STRATEGIES FOR ACUTE RESPIRATORY FAILURE

W hile our basic understanding of the pathophysiology of acute respiratory failure (ARF) is steadily improving, optimal management of surgical patients with ARF remains controversial.’ For many of the commonly used modalities, there is insufficient data to conclusively state that one is better than the other. Thus, local expert opinion prevails and typically surgeons are excluded from establishing institutional policies which undermines their autonomy in the management of complex ICU patients. Consequently, when reorganizing our Surgical Intensive Care Unit at Denver General Hospital in 1986, we developed practice guidelines (Figure 1) that defined our standard approach as well as the sequence of alternatives (some unconventional). Additionally, we created a clinical specialist position to insure guideline implementation as well as ongoing assessment and revision. This chapter will focus on the intubated surgical patient who requires mechanical ventilation and will specifically address (1) methods to improve oxygenation, (2) methods to assure ventilation, and (3) other nonventilator alternatives that we have found useful in our patient population.

Ultrasound-guided supraclavicular access to the innominate vein for central venous cannulation.

C of the innominate (brachiocephalic) vein for central venous access has been described since the 1950s; however, the consistency of anatomic, landmark-based percutaneous cannulation of the internal jugular, subclavian, or femoral vein overshadowed the use of this vessel historically. Infection rates persistently as high as 4 or 6 per 1,000 catheter days for subclavian or internal jugular vein catheters, respectively, in some studies and thrombosis rates more than 40% in other series have prompted scrutiny and consideration of the optimal method and location for central venous access. The advent of routine use of ultrasound for central venous line placement has further renewed interest in exploring alternative access sites. The supraclavicular approach using ultrasound guidance has been shown to be advantageous in the pediatric patient population with small vessels. In a recent case-controlled study of patients with reduced intracranial compliance, cannulation of the innominate vein with ultrasound guidance proved efficacious and successful without placement into the Trendelenburg position. Thus, we hypothesized that using standard sterile technique and ultrasound guidancewhile cannulating the innominate vein via a supraclavicular approach would result in a low infection and thrombotic rate observed with a subclavian line while maintaining the complication rate associated with an internal jugular vein cannulation. The purpose of this report was to describe an ultrasound-based supraclavicular approach to the innominate vein.