James M. Isbell

Damage control hematology: The impact of a trauma exsanguination protocol on survival and blood product utilization

BACKGROUND The importance of early and aggressive management of trauma- related coagulopathy remains poorly understood. We hypothesized that a trauma exsanguination protocol (TEP) that systematically provides specified numbers and types of blood components immediately upon initiation of resuscitation would improve survival and reduce overall blood product consumption among the most severely injured patients. METHODS We recently implemented a TEP, which involves the immediate and continued release of blood products from the blood bank in a predefined ratio of 10 units of packed red blood cells (PRBC) to 4 units of fresh frozen plasma to 2 units of platelets. All TEP activations from February 1, 2006 to July 31, 2007 were retrospectively evaluated. A comparison cohort (pre-TEP) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. Multivariable analysis was performed to compare mortality and overall blood product consumption between the two groups. RESULTS Two hundred eleven patients met inclusion criteria (117 pre-TEP, 94 TEP). Age, sex, and Injury Severity Score were similar between the groups, whereas physiologic severity (by weighted Revised Trauma Score) and predicted survival (by trauma-related Injury Severity Score, TRISS) were worse in the TEP group (p values of 0.037 and 0.028, respectively). After controlling for age, sex, mechanism of injury, TRISS and 24-hour blood product usage, there was a 74% reduction in the odds of mortality among patients in the TEP group (p = 0.001). Overall blood product consumption adjusted for age, sex, mechanism of injury, and TRISS was also significantly reduced in the TEP group (p = 0.015). CONCLUSIONS We have demonstrated that an exsanguination protocol, delivered in an aggressive and predefined manner, significantly reduces the odds of mortality as well as overall blood product consumption.

Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival.

BACKGROUND Despite recent attention and impressive results with damage control resuscitation, the appropriate ratio of blood products to be transfused has yet to be defined. The purpose of this study was to evaluate whether suggested blood product ratios yield superior survival rates. MATERIALS After IRB approval, a retrospective evaluation was performed on all trauma exsanguination protocol (TEP, n = 118) activations from February 1, 2006 to July 31, 2007. A comparison cohort (pre-TEP, n = 140) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. We then compared those who received FFP:RBC (2:3) and platelet:RBC (1:5) ratios with those who did not reach these ratios. Multivariate analysis was performed for independent predictors of mortality. RESULTS A total of 259 patients were available for study. Patients receiving FFP:RBC at a ratio of 2:3 or greater (n = 64) had a significant reduction in 30-day mortality compared with those who received less than a 2:3 ratio (n = 195); 41% versus 62%, p = 0.008. Patients receiving platelets:RBC at a ratio of 1:5 or greater (n = 63) had a lower 30-day mortality when compared with those with who received less than this ratio (n = 196); (38% vs. 61%, p = 0.001). Regression model demonstrated that a ratio of FFP to PRBC is an independent predictor of 30-day mortality, controlling for age and TRISS (OR 1.78, 95% CI 1.01-3.14). CONCLUSIONS Increased FFP:PRBC and PLT:PRBC ratios during a period of massive transfusion improved survival after major trauma. Massive transfusion protocols should be designed to achieve these ratios to provide maximal benefit.

The Importance of Caloric Restriction in the Early Improvements in Insulin Sensitivity After Roux-en-Y Gastric Bypass Surgery

OBJECTIVE Many of the metabolic benefits of Roux-en-Y gastric bypass (RYGB) occur before weight loss. In this study we investigated the influence of caloric restriction on the improvements in the metabolic responses that occur within the 1st week after RYGB. RESEARCH METHODS AND DESIGN A mixed meal was administered to nine subjects before and after RYGB (average 4 ± 0.5 days) and to nine matched, obese subjects before and after 4 days of the post-RYGB diet. RESULTS Weight loss in both groups was minimal; the RYGB subjects lost 1.4 ± 5.3 kg (P = 0.46) vs. 2.2 ± 1.0 kg (P = 0.004) in the calorically restricted group. Insulin resistance (homeostasis model assessment of insulin resistance) improved with both RYGB (5.0 ± 3.1 to 3.3 ± 2.1; P = 0.03) and caloric restriction (4.8 ± 4.1 to 3.6 ± 4.1; P = 0.004). The insulin response to a mixed meal was blunted in both the RYGB and caloric restriction groups (113 ± 67 to 65 ± 33 and 85 ± 59 to 65 ± 56 nmol · l−1 · min−1, respectively; P < 0.05) without a change in the glucose response. Glucagon-like peptide 1 levels increased (9.2 ± 8.6 to 12.2 ± 5.5 pg · l−1 · min−1; P = 0.04) and peaked higher (45.2 ± 37.3 to 84.8 ± 33.0 pg/ml; P = 0.01) in response to a mixed meal after RYGB, but incretin responses were not altered after caloric restriction. CONCLUSIONS These data suggest that an improvement in insulin resistance in the 1st week after RYGB is primarily due to caloric restriction, and the enhanced incretin response after RYGB does not improve postprandial glucose homeostasis during this time.

Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery

Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.

Roux-en-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics.

BACKGROUND Obesity and type 2 diabetes are associated with renal dysfunction, which improves after Roux-en-Y gastric bypass (RYGB). During a 12-month follow-up period, we studied prospectively the changes in glomerular and tubular functions that occurred in excessively obese diabetic and non diabetic subjects after RYGB. METHODS The cohort included 35 patients, 54% of whom had type 2 diabetes. Glomerular filtration rate (GFR) was estimated using creatinine clearance. Tubular function was studied by measuring the ratio of urinary cystatin C to urinary creatinine (UCC ratio). RESULTS Baseline renal parameters, anthropometric characteristics, and changes in body mass index after the surgical procedures were similar between the 2 cohorts. At 12 months after RYGB, creatinine clearance decreased 15% in diabetics (P = .02) and 21% in nondiabetics (P = .03). A change in GFR was seen earlier in the nondiabetics (-29% after 6 months; P = .003). The UCC ratio was increased at both 6- and 12-month follow-ups (P = .03 and .003, respectively) only in the diabetic group. CONCLUSION GFR was improved at 12 months after RYGB, with nondiabetics showing a greater propensity score. Tubular function remained unchanged in the nondiabetic subjects, but worsening occurred in the diabetic subjects. These results underscore the importance of reversal of excessive obesity before the onset of frank diabetes.

Effects of Proximal Gut Bypass on Glucose Tolerance and Insulin Sensitivity in Humans

Roux-en-Y gastric bypass (RYGB) surgery produces a significant improvement in glucose metabolism prior to substantial weight loss; this is proposed to result from an enhanced incretin effect secondary to bypass of the duodenum and proximal jejunum. However, the caloric restriction that occurs early after surgery also has beneficial metabolic effects. To dissect the contribution of nutrient bypass of the proximal gut to improved glucose tolerance after RYGB surgery from caloric restriction, we induced a “non-surgical, proximal gut bypass” by directly administering a glucose load to the jejunum via a nasally inserted feeding tube. We studied 10 obese participants (BMI = 41.3 ± 7.4 kg/m2; 36 ± 9 years; 60% female; HbA1c = 5.5 ± 0.5%) on two occasions. At each visit, a 50-g glucose load was administered to either the stomach or proximal jejunum in random order. Blood was sampled −10, 0, 2, 4, 6, 8, …