Assessment of resuscitation as measured by markers of metabolic acidosis and features of injury.

AIMS: The best time for definitive orthopaedic care is often unclear in patients with multiple injuries. The objective of this study was make a prospective assessment of the safety of our early appropriate care (EAC) strategy and to evaluate the potential benefit of additional laboratory data to determine readiness for surgery. PATIENTS AND METHODS: A cohort of 335 patients with fractures of the pelvis, acetabulum, femur, or spine were included. Patients underwent definitive fixation within 36 hours if one of the following three parameters were met: lactate < 4.0 mmol/L; pH ≥ 7.25; or base excess (BE) ≥ -5.5 mmol/L. If all three parameters were met, resuscitation was designated full protocol resuscitation (FPR). If less than all three parameters were met, it was designated an incomplete protocol resuscitation (IPR). Complications were assessed by an independent adjudication committee and included infection; sepsis; PE/DVT; organ failure; pneumonia, and acute respiratory distress syndrome (ARDS). RESULTS: In total, 66 patients (19.7%) developed 90 complications. An historical cohort of 1441 patients had a complication rate of 22.1%. The complication rate for patients with only one EAC parameter at the point of protocol was 34.3%, which was higher than other groups (p = 0.041). Patients who had IPR did not have significantly more complications (31.8%) than those who had FPR (22.6%; p = 0.078). Regression analysis showed male gender and injury severity score to be independent predictors of complications. CONCLUSIONS: This study highlights important trends in the IPR and FPR groups, suggesting that differences in resuscitation parameters may guide care in certain patients; further study is, however, required. We advocate the use of the existing protocol, while research is continued for high-risk subgroups. Cite this article: Bone Joint J 2017;99-B:122-7.

Is Early Appropriate Care of axial and femoral fractures appropriate in multiply-injured elderly trauma patients?

BACKGROUND: Previous work established resuscitation parameters that minimize complications with early fracture management. This Early Appropriate Care (EAC) protocol was applied to patients with advanced age to determine if they require unique parameters to mitigate complications. METHODS: Between October 2010 and March 2013, 376 consecutive skeletally mature patients with unstable fractures of the pelvis, acetabulum, thoracolumbar spine, and/or proximal or diaphyseal femur fractures were treated at a level I trauma center and were prospectively studied. Patients aged ≤30 years (n = 114), 30 to 60 years (n = 184), and ≥60 years (n = 37) with Injury Severity Scores (ISS) ≥16 and unstable fractures of the pelvis, acetabulum, spine, and/or diaphyseal femur were treated within 36 h, provided they showed evidence of adequate resuscitation. ISS, Glasgow Coma Scale (GCS), and American Society of Anesthesiologists (ASA) classification were determined. Lactate, pH, and base excess (BE) were measured at 8-h intervals. Complications included pneumonia, pulmonary embolism (PE), acute renal failure, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), deep vein thrombosis, infection, sepsis, and death. RESULTS: Patients ≤30 years old (y/o) were more likely to sustain gunshot wounds (p = 0.039), while those ≥60 y/o were more likely to fall from a height (p = 0.002). Complications occurred at similar rates for patients ≤30 y/o, 30 to 60 y/o, and ≥60 y/o. There were no differences in lactate, pH, or BE at the time of surgery. For patients ≤30 y/o, there were increased overall complications if pH was <7.30 (p = 0.042) or BE <-6.0 (p = 0.049); patients ≥60 y/o demonstrated more sepsis if BE was <-6.0 (p = 0.046). CONCLUSIONS: EAC aims to definitively manage axial and femoral shaft fractures once patients have been adequately resuscitated to minimize complications. EAC is associated with comparable complication rates in young and elderly patients. Further study is warranted with a larger sample to further validate EAC in elderly patients. LEVEL OF EVIDENCE: level II prospective, comparative study.

Inhibition of heme oxygenase after oral vs intraperitoneal administration of chromium porphyrins.

The effects of chromium porphyrins on suckling rat heme oxygenase activity were compared following oral vs intraperitoneal dosing. Chromium protoporphyrin (CrPP), chromium mesoporphyrin (CrMP), or chromium deuteroporphyrin 2,4 bis glycol (CrBG) were administered at 40 mumol/kg to 2-week old suckling rats either orally or intraperitoneally. Six hours after intraperitoneal dosing, CrPP and CrMP had significantly reduced hepatic and splenic heme oxygenase activity by more than 55%. CrBG effectively reduced hepatic heme oxygenase activity by 42%. More importantly, only CrMP was an effective inhibitor of hepatic heme oxygenase activity 6 hr after oral administration. In the first reported comparison of chromium porphyrin efficacy in vivo, our data suggest that chromium porphyrins, and particularly CrMP, may be effective in chemopreventive strategies for the treatment of neonatal jaundice.

Absorption of zinc deuteroporphyrin IX 2,4-bis-glycol by the neonatal rat small intestine in vivo.

Zinc deuteroporphyrin IX 2,4-bis-glycol (ZnBG) is a potent inhibitor of heme oxygenase and may be useful in the prevention of neonatal jaundice. Enteral administration could be advantageous clinically, but it has been only minimally effective with other metalloporphyrins in rats and humans. Thus, the absorption of ZnBG by the small intestine in vivo was examined. ZnBG was administered enterally at 40 mumol/kg to 2-week-old suckling rats via in situ catheterization of the small intestine. Within 15 min ZnBG was absorbed by the small intestine, as it was measured in portal and systemic venous plasma, intestine, kidney, liver, and spleen. Concentrations exceeding 5.0 microM were found in plasma within 30 min, and 9.4 microM was found in the liver after 30 min. A total of 4.6% of the administered ZnBG dose was measured in plasma and tissues.

Oral administration of zinc deuteroporphyrin IX 2,4 bis glycol inhibits heme oxygenase in neonatal rats.

Zinc deuteroporphyrin IX 2,4 bis glycol (ZnBG) has been shown to be a potent inhibitor of heme oxygenase (HO) in vitro. Oral administration, which has been minimally effective with other metalloporphyrins, could be clinically advantageous for prevention of neonatal hyperbilirubinemia. Therefore, we examined the effect of oral administration of ZnBG on tissue HO activity and tissue ZnBG concentrations. Suckling rats at 2 weeks of age received ZnBG at 40 mumol/kg BW via gastric gavage. Rats were killed with anesthetic over-dose after 60 min. ZnBG was detected in the portal and systemic circulation (n = 12), and the liver, kidney, spleen, and intestine (n = 8). ZnBG concentrations of 7.9 nmol/g liver and 1.7 nmol/g spleen corresponded to 67 and 72% inhibition of control HO activity (n = 9; p less than 0.0005) respectively.