Coagulopathy leading to excessive blood loss is a serious complication of cardiac surgery. In this prospective cohort study, we measured patients' coagulation status before and after cardiopulmonary bypass (CPB) and examined their relationships with postoperative blood loss.Patients undergoing complex cardiac surgery with CPB who did not have preexisting coagulopathy were eligible. Detailed clinical and coagulation data were prospectively collected on all patients. Coagulation testing was performed before and after CPB, and included measures of thrombin generation, clotting factor consumption and dilution, clot stabilization, and fibrinolysis. The associations of variables with post-CPB blood loss (estimated loss from CPB to intensive care unit admission and 24-hour chest tube drainage) were assessed with the Spearman rank correlation test and multivariable linear regression.The median blood loss among the 101 study patients was 952 mL (interquartile range, 601-1553 mL). Variables independently associated with increasing blood loss were as follows: previous sternotomies (P = 0.01), lower pre-CPB prothrombin fragment F1 + 2 levels (measure of thrombin generation; P = 0.001), lower post-CPB platelet counts (P = 0.01), larger percent decrease in fibrinogen levels (P = 0.05), and higher post-CPB soluble fibrin monomer levels (measure of thrombin activity and clot stabilization; P < 0.0001) (model R(2) = 0.43).In complex cardiac surgery, blood loss is directly influenced by reduced pre-CPB thrombin generation rate, increased post-CPB consumption and dilution of clotting factors, as well as inadequate post-CPB clot stabilization. This information can aid in identifying patients at high risk for excessive blood loss and testing new interventions aimed at reducing the burden of this complication. The validity and generalizability of these findings need to be assessed by other studies.
Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients.
Background: Enhanced recovery after surgery (ERAS) programs incorporate evidence-based practices to minimize perioperative stress, gut dysfunction, and promote early recovery. However, it is unknown which components have the greatest impact. Objective: This study aims to determine which components of ERAS programs have the largest impact on recovery for patients undergoing colorectal surgery. Methods: An iERAS program was implemented in 15 academic hospitals. Data were collected prospectively. Patients were considered compliant if >75% of the preoperative, intraoperative, and postoperative predefined interventions were adhered to. Optimal recovery was defined as discharge within 5 days of surgery with no major complications, no readmission to hospital, and no mortality. Multivariable analysis was used to model the impact of compliance and technique on optimal recovery. Results: Overall, 2876 patients were enrolled. Colon resections were performed in 64.7% of patients and 52.9% had a laparoscopic procedure. Only 20.1% of patients were compliant with all phases of the pathway. The poorest compliance rate was for postoperative interventions (40.3%) which was independently associated with an increase in optimal recovery (RR = 2.12, 95% CI 1.81–2.47). Compliance with ERAS interventions remained associated with improved outcomes whether surgery was performed laparoscopically (RR = 1.55, 95% CI 1.23–1.96) or open (RR = 2.29, 95% CI 1.68–3.13). However, the impact of ERAS compliance was significantly greater in the open group ( P < 0.001). Conclusions: Postoperative compliance is the most difficult to achieve but is most strongly associated with optimal recovery. Although our data support that ERAS has more effect in patients undergoing open surgery, it also showed a significant impact on patients treated with a laparoscopic approach.
We studied the role of donor and recipient age in transplantation/ischemia-reperfusion injury (TIRI) and short- and long-term graft and patient survival. Eight hundred twenty-two patients underwent deceased donor liver transplantation, with 197 donors being > or = 60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short- and long-term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3- and 5-year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients > or = 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3- and 5-year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3- and 5-year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients.
BackgroundThe Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications.MethodsThe analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes.ResultsThe DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96–0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92–0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00–1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01–1.05).ConclusionsA DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.
Heme biosynthesis in hepatocytes is controlled by a free heme pool, which regulates δ-aminolevulinic acid synthase. Porphyrinogenic chemicals deplete the regulatory free heme pool by interacting with cytochrome P-450 thereby inhibiting heme biosynthesis and/or causing heme breakdown. Recent developments allow us to predict which groups of chemicals are likely to be porphyrinogenic. One group is exemplified by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine. Heterocyclic compounds of this type cause mechanism-based inactivation of cytochrome P-450, leading to the formation of N-alkylporphyrins, with ferrochelatase-inhibitory activity resulting in lowering the free heme pool. Allylisopropylacetamide exemplifies a second group. Such compounds containing a terminal olefinic or acetylenic group, cause mechanism-based inactivation of cytochrome P-450. In the process, the heme moiety of cytochrome P-450 is destroyed and the free heme pool is lowered. A third group is exemplified by planar polyhalogenated or polycyclic aromatic hydrocarbons. These compounds induce specific cytochrome P-450 isozymes but are poor substrates. Active oxygen is formed, which interacts with a hepatic substrate to form a uroporphyrinogen decarboxylase inhibitor. Inhibition of this enzyme leads to depletion of the free heme pool.—Marks, G. S.; McCluskey, S. A.; Mackie, J. E.; Riddick, D. S.; James, C. A. Disruption of hepatic heme biosynthesis after interaction of xenobiotics with cytochrome P-450. FASEB J. 2: 2774-2783; 1988.
