Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery

PURPOSE: To determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery. METHODS: In this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis. RESULTS: Of the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets - 1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events. CONCLUSIONS: Transfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.     

From divination to madness: features of acute intoxication with Salvia use

Salvia divinorum is a psychoactive botanical plant that is increasingly used for the ‘legal’ highs that it can produce. It is readily available for purchase on the Internet, and most abusers are unaware of the toxicity and abuse potential associated with its use. As the use of novel compounds among abusers is not uncommon, physicians need to increase their awareness and recognition of these new substances. Herein, we report a case of an acute presentation of Salvia intoxication.     

A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study

Purpose

Clonidine may help prevent cardiac complications in patients undergoing non-cardiac surgery and receiving chronic beta-blocker therapy. We conducted a multicentre pilot randomized trial to estimate recruitment rates for a full-scale trial and to assess the safety and tolerability of combining clonidine with chronic beta-blockade.

Methods

Patients who were at elevated perioperative cardiac risk, receiving chronic beta-blockade, and scheduled for major non-cardiac surgery were recruited in a blinded (participants, clinicians, outcome assessors) placebo-controlled randomized trial at three Canadian hospitals. Participants were randomized to clonidine (0.2 mg oral tablet one hour before surgery, plus 0.2 mg·day^?1 transdermal patch placed one hour before surgery and removed four days after surgery or hospital discharge, whichever came first) or matching placebo. Feasibility was evaluated based on recruitment rates, with each centre being required to recruit 50 participants within 12-18 months. Additionally, we reviewed study drug withdrawals and safety outcomes, including clinically significant hypotension or bradycardia.

Results

Eighty-two of the 168 participants were randomized to receive clonidine and 86 to receive placebo. The average time to recruit 50 participants at each centre was 14.3 months. Six patients (7%) withdrew from clonidine, while four (5%) withdrew from placebo. Based on qualitative review, there were no major safety concerns related to clonidine. There was a moderate overall rate of cardiac morbidity, with 18 participants (11%) suffering postoperative myocardial infarction.

Conclusion

This pilot randomized trial confirmed the feasibility, safety, and tolerability of a full-scale trial of oral and transdermal clonidine for reducing the risk of cardiac complications during non-cardiac surgery. This trial was registered at www.clinicaltrials.gov: NCT00335582.     

SaOS2 Osteosarcoma Cells as an In Vitro Model for Studying the Transition of Human Osteoblasts to Osteocytes

The central importance of osteocytes in regulating bone homeostasis is becoming increasingly apparent. However, the study of these cells has been restricted by the relative paucity of cell line models, especially those of human origin. Therefore, we investigated the extent to which SaOS2 human osteosarcoma cells can differentiate into osteocyte-like cells. During culture under the appropriate mineralising conditions, SaOS2 cells reproducibly synthesised a bone-like mineralised matrix and temporally expressed the mature osteocyte marker genes SOST, DMP1, PHEX and MEPE and down-regulated expression of RUNX2 and COL1A1. SaOS2 cells cultured in 3D collagen gels acquired a dendritic morphology, characteristic of osteocytes, with multiple interconnecting cell processes. These findings suggest that SaOS2 cells have the capacity to differentiate into mature osteocyte-like cells under mineralising conditions. PTH treatment of SaOS2 cells resulted in strong down-regulation of SOST mRNA expression at all time points tested. Interestingly, PTH treatment resulted in the up-regulation of RANKL mRNA expression only at earlier stages of differentiation. These findings suggest that the response to PTH is dependent on the differentiation stage of the osteoblast/osteocyte. Together, our results demonstrate that SaOS2 cells can be used as a human model to investigate responses to osteotropic stimuli throughout differentiation to a mature osteocyte-like stage.     

Serum tocopherols, selenium and lung cancer risk among tin miners in China

Objective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case–control study nested in an occupational cohort of tin miners. Methods: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Results: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Conclusion: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.     

Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies

OBJECTIVES: The purpose of this study was to assess the effects of off-pump coronary bypass surgery (OPCAB) on mortality and morbidity. BACKGROUND: Despite its potential for reducing morbidity and mortality, OPCAB's role in clinical practice remains controversial. METHODS: A meta-analysis of 37 randomized controlled trials (RCTs) (n = 3,449) and 22 risk-adjusted (logistic regression or propensity-score) observational studies (n = 293,617) was performed. Two reviewers performed literature searches (MEDLINE, EMBASE, PubMed, reference lists), quality assessment, and data extraction. Treatment effects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In RCTs, OPCAB was associated with reduced atrial fibrillation (OR 0.59; 95% CI 0.46 to 0.77) and trends toward reduced 30-day mortality (OR 0.91 95% CI 0.45 to 1.83), stroke (OR 0.52; 95% CI 0.25 to 1.05), and myocardial infarction (OR 0.79; 95% CI 0.50 to 1.25). Observational studies showed OPCAB to be associated with reduced 30-day mortality (OR 0.72; 95% CI 0.66 to 0.78), stroke (OR 0.62; 95% CI 0.55 to 0.69), infarction (OR 0.66; 95% CI 0.50 to 0.88), and atrial fibrillation (OR 0.78; 95% CI 0.74 to 0.82). At one to two years, OPCAB was associated with trends toward reduced mortality, but also increased repeat revascularization (RCT: OR 1.75, 95% CI 0.78 to 3.94; Observational: OR 1.35, 95% CI 0.76 to 2.39). CONCLUSIONS: Randomized controlled trials did not find, aside from atrial fibrillation, the statistically significant reductions in short-term mortality and morbidity demonstrated by observational studies. These discrepancies might be due to differing patient-selection and study methodology. Future studies must focus on improving research methodology, recruiting high-risk patients, and collecting long-term data.     

Calcium antagonists are associated with reduced mortality after cardiac surgery: a propensity analysis

OBJECTIVES: Observational studies have questioned the effectiveness of perioperative calcium channel blockers but failed to correct for selection biases. We therefore performed a prospective observational cohort study of the effects of calcium channel blockers on cardiac surgical mortality. A propensity score technique was used for risk adjustment. METHODS: We identified 6619 patients who underwent nontransplant cardiac surgery at the Toronto General Hospital (Toronto, Ontario, Canada) between May 1999 and December 2001. Propensity scores for calcium channel blocker use were constructed for the entire sample and for the subgroup (n = 5222) that underwent coronary artery bypass grafting. The calcium channel blocker adjusted odds ratio for in-hospital mortality after cardiac surgery was determined by using multiple logistic regression and propensity matched-pairs analyses. A subgroup analysis was performed for patients who underwent coronary artery bypass grafting: the calcium channel blocker adjusted odds ratio for mortality was determined by using propensity score matched-pairs analyses. RESULTS: Calcium channel blockers were associated with significantly reduced cardiac surgical mortality after adjustment with both multiple logistic regression (odds ratio, 0.56; 95% confidence interval, 0.33-0.94; P =.028) and propensity score matched-pairs analyses (odds ratio, 0.56; 95% confidence interval, 0.32-0.98; P =.042). Calcium channel blockers were also associated with reduced mortality (odds ratio, 0.48; 95% confidence interval, 0.23-0.98; P =.044) among patients who underwent coronary artery bypass grafting. CONCLUSIONS: After adjustment for baseline differences, calcium channel blockers were associated with significantly reduced mortality after cardiac surgery. This benefit also extends to the subgroup that underwent coronary artery bypass grafting. A large randomized controlled trial of perioperative calcium channel blockers is therefore warranted.     

Survival pattern in patients with acute organophosphate poisoning receiving intensive care

BACKGROUND: Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. METHODS: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. RESULTS: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. CONCLUSION: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.     

Calcium channel blockers for reducing cardiac morbidity after noncardiac surgery: a meta-analysis

Cardiac complications are the leading cause of death after noncardiac surgery. Despite theoretical benefits, calcium channel blockers (CCB) are not widely used in the perioperative setting. This systematic review assessed the efficacy of CCBs during noncardiac surgery. MEDLINE, EMBASE, Science Citation Index, PubMed, and reference lists were searched without language restriction for randomized controlled trials (RCT) evaluating CCBs during noncardiac surgery. Two reviewers independently abstracted data on death, myocardial infarction (MI), ischemia, supraventricular tachyarrhythmia (SVT), and congestive heart failure (CHF). Treatment effects were calculated as relative risks (RR) with 95% confidence intervals (CI). Eleven studies (1007 patients) were included. CCBs significantly reduced ischemia (RR, 0.49; 95% CI, 0.30-0.80; P = 0.004) and SVT (RR, 0.52; 95% CI, 0.37-0.72; P < 0.0001). CCBs were associated with trends towards reduced death and MI. In post hoc analyses, CCBs significantly reduced death/MI (RR, 0.35; 95% CI, 0.15-0.86; P = 0.02) and major morbid events (MME), defined as death, MI, or CHF (RR, 0.39; 95% CI, 0.17-0.89; P = 0.02). In subgroup analyses, diltiazem significantly reduced ischemia, SVT, death/MI, and MMEs. This meta-analysis shows CCBs significantly reduced ischemia, SVT, and combined end-points in the setting of noncardiac surgery. The majority of these benefits are attributable to diltiazem, suggesting the need for further evaluation of this drug in a large RCT.