Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Uncontrolled pain after noncardiac surgery activates the sympathetic nervous system, which causes tachycardia, hypertension, and increased cardiac contractility-all of which may increase myocardial oxygen demand. We therefore determined whether time-weighted average pain scores over the initial 72 postoperative hours are associated with myocardial injury after noncardiac surgery (MINS). METHODS: We conducted a retrospective cohort analysis of adults with routine postoperative troponin monitoring after noncardiac surgery under general, regional, or combined anesthesia at tertiary level centers in Cleveland from January 2012 to December 2015. Time-weighted average pain scores were calculated from all the available pain scores, typically at 4-hour intervals, until a troponin elevation was detected. MINS was defined as peak troponin T concentrations exceeding 0.03 ng/mL within 72 hours after surgery. We used a generalized linear mixed model to assess the association between pain and MINS with 3 hospitals as clusters, adjusting for potential confounders. RESULTS: Among 2892 eligible patients, 4.5% had myocardial injury within 72 hours after surgery. Higher time-weighted average pain scores were associated with increased hazard of myocardial injury. The estimated hazard ratio for a 1-unit increase in pain score was 1.12 (95% confidence interval [CI], 1.02-1.22; P = .013), adjusting for confounding variables. CONCLUSIONS: Among patients undergoing noncardiac surgery, time-weighted average pain scores within 72 hours after surgery were significantly associated with myocardial injury.

Association Between Mean Arterial Pressure and Acute Kidney Injury and a Composite of Myocardial Injury and Mortality in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis.

OBJECTIVES: Hypotension thresholds that provoke renal injury, myocardial injury, and mortality in critical care patients remain unknown. We primarily sought to determine the relationship between hypotension and a composite of myocardial injury (troponin T ≥ 0.03 ng/mL without nonischemic cause) and death up to 7 postoperative days. Secondarily, we considered acute kidney injury (creatinine concentration ≥ 0.3 mg/dL or 1.5 times baseline). DESIGN: Retrospective cohort. SETTING: Surgical ICU at an academic medical center. PATIENTS: Two-thousand eight-hundred thirty-three postoperative patients admitted to the surgical ICU. INTERVENTIONS: A Cox proportional hazard survival model was used to assess the association between lowest mean arterial pressure on each intensive care day, considered as a time-varying covariate, and outcomes. In sensitivity analyses hypotension defined as pressures less than 80 mm Hg and 70 mm Hg were also considered. MEASUREMENTS AND MAIN RESULTS: There was a strong nonlinear (quadratic) association between the lowest mean arterial pressure and the primary outcome of myocardial injury after noncardiac surgery or mortality, with estimated risk increasing at lower pressures. The risk of myocardial injury after noncardiac surgery or mortality was an estimated 23% higher at the 25th percentile (78 mm Hg) of lowest mean arterial pressure compared with at the median of 87 mm Hg, with adjusted hazard ratio (95% CI) of 1.23 (1.12-1.355; p < 0.001). Overall results were generally similar in sensitivity analyses based on every hour of mean arterial pressure less than 80 mm Hg and any mean arterial pressure less than 70 mm Hg. Post hoc analyses showed that the relationship between ICU hypotension and outcomes depended on the amount of intraoperative hypotension. The risk of acute kidney injury increased over a range of minimum daily pressures from 110 mm Hg to 50 mm Hg, with an adjusted hazard ratio of 1.27 (95% CI, 1.18-1.37; p < 0.001). CONCLUSIONS: Increasing amounts of hypotension (defined by lowest mean arterial pressures per day) were strongly associated with myocardial injury, mortality, and renal injury in postoperative critical care patients.

Intraoperative Hyperoxia Does Not Reduce Postoperative Pain: Subanalysis of an Alternating Cohort Trial.

BACKGROUND: Postoperative pain is common and promotes opioid use. Surgical wounds are hypoxic because normal perfusion is impaired. Local wound ischemia and acidosis promote incisional pain. Some evidence suggests that improving oxygen supply to surgical wounds might reduce pain. We therefore tested the hypothesis that supplemental (80% inspired) intraoperative oxygen reduces postoperative pain and opioid consumption. METHODS: We conducted a post hoc analysis of a large, single-center alternating cohort trial allocating surgical patients having general anesthesia for colorectal surgery to either 30% or 80% intraoperative oxygen concentration in 2-week blocks for a total of 39 months. Irrespective of allocation, patients were given sufficient oxygen to maintain saturation ≥95%. Patients who had regional anesthesia or nerve blocks were excluded. The primary outcome was pain and opioid consumption during the initial 2 postoperative hours, analyzed jointly. The secondary outcome was pain and opioid consumption over the subsequent 24 postoperative hours. Subgroup analyses of the primary outcome were conducted for open versus laparoscopic procedures and for patients with versus without chronic pain. RESULTS: A total of 4702 cases were eligible for analysis: 2415 were assigned to 80% oxygen and 2287 to 30% oxygen. The groups were well balanced on potential confounding factors. Average pain scores and opioid consumption were similar between the groups (mean difference in pain scores, -0.01 [97.5% CI, -0.16 to 0.14; P = .45], median difference in opioid consumption, 0.0 [97.5% CI, 0 to 0] mg morphine equivalents; P = .82). There were also no significant differences in the secondary outcome or subgroup analyses. CONCLUSIONS: Supplemental intraoperative oxygen does not reduce acute postoperative pain or reduce opioid consumption.

The Association Between Timing of Routine Preoperative Blood Testing and a Composite of 30-Day Postoperative Morbidity and Mortality.

BACKGROUND: Laboratory testing is a common component of preanesthesia evaluation and is designed to identify medical abnormalities that might otherwise remain undetected. While blood testing might optimally be performed shortly before surgery, it is often done earlier for practical reasons. We tested the hypothesis that longer periods between preoperative laboratory testing and surgery are associated with increased odds of having a composite of 30-day morbidity and mortality. METHODS: We obtained preoperative data from 2,320,920 patients in the American College of Surgeons National Surgical Quality Improvement Program who were treated between 2005 and 2012. Our analysis was restricted to relatively healthy patients with American Society of Anesthesiology physical status I-II who had elective surgery and normal blood test results (n = 235,010). The primary relationship of interest was the odds of 30-day morbidity and mortality as a function of delay between preoperative testing and surgery. A multivariable logistic regression model was used for the 10 pairwise comparisons among the 5 laboratory timing groups (laboratory blood tests within 1 week of surgery; 1-2 weeks; 2-4 weeks; 1-2 months; and 2-3 months) on 30-day morbidity, adjusting for any imbalanced baseline covariables and type of surgery. RESULTS: A total of 4082 patients (1.74%) had at least one of the component morbidities or died within 30-days after surgery. The observed incidence (unadjusted) was 1.7% when the most recent laboratory blood tests measured within 1 week of surgery, 1.7% when it was within 1-2 weeks, 1.8% when it was within 2-4 weeks, 1.7% when it was between 1 and 2 months, and 2.0% for patients with most recent laboratory blood tests measured 2-3 months before surgery. None of the values within 2 months differed significantly: estimated odds ratios for patients within blood tested within 1 week were 1.00 (99.5% confidence interval, 0.89-1.12) as compared to 1-2 weeks, 0.88 (0.77-1.00) for 2-4 weeks, and 0.95 (0.79-1.14) for 1-2 months, respectively. The estimated odds ratio comparing 1-2 weeks to each of 2-4 weeks and 1-2 months were 0.88 (0.76-1.03) and 0.95 (0.78-1.16), respectively. Blood testing 2-3 months before surgery was associated with increased odds of outcome compared to patients whose most recent test was within 1 week (P = .002) and 1-2 weeks of the date of surgery. CONCLUSIONS: In American Society of Anesthesiologists physical status I and II patients, risk of 30-day morbidity and mortality was not different with blood testing up to 2 months before surgery, suggesting that it is unnecessary to retest patients shortly before surgery.

Mild Perioperative Hypothermia and Myocardial Injury: A Retrospective Cohort Analysis.

BACKGROUND: We tested the primary hypothesis that final intraoperative esophageal temperature is associated with increased odds of a composite of in-hospital all-cause mortality and myocardial injury within 7 days after noncardiac surgery. Secondary exposures were time-weighted average intraoperative temperature and area <37°C threshold. METHODS: Myocardial injury was defined by postoperative fourth-generation troponin T ≥0.03 ng/mL apparently due to cardiac ischemia. Data were extracted for inpatients who had noncardiac surgery with general anesthesia at the Cleveland Clinic between 2012 and 2015. All had esophageal temperature monitoring and routine postoperative troponin monitoring. We estimated the confounder-adjusted association between final intraoperative esophageal temperature and the collapsed composite with multivariable logistic regression. We similarly estimated associations with time-weighted average intraoperative temperature and area <37°C. RESULTS: Two thousand two hundred ten patients were included. Nearly all final esophageal temperatures were 36°C-37°C. Ninety-seven patients (4.4%) had myocardial injury, and 7 (0.3%) died before discharge. Final intraoperative core temperature was not associated with the collapsed composite: odds ratio, 0.91 (95% confidence interval, 0.68-1.24) per 1°C decrease. Similarly, neither of the secondary exposures was associated with the composite outcome. CONCLUSIONS: We did not observe an association between mild perioperative hypothermia and mortality or myocardial injury in adults having noncardiac surgery. However, the range of final intraoperative temperatures was small and largely restricted to the normothermic range (36°C-37°C). Trials are needed to further assess the effect of temperature on myocardial injury.

A multicenter survey on toxoplasmosis knowledge among pregnant women in Poland (the TOWER study).

BACKGROUND: The seroprevalence of Toxoplasma gondii ranges widely in different areas of the world and different populations. Although toxoplasmosis is typically benign and asymptomatic, it induces major complications in immunocompromised individuals and during pregnancy. Prevention of maternal primary infection constitutes the major tool for avoiding congenital T. gondii infections and toxoplasmosis complications. The preventive measures depend on the women's knowledge about toxoplasmosis. The aim of the study was to assess the knowledge on toxoplasmosis among pregnant women in Poland. METHODS: The study was conducted between October 2016 and January 2017 in 3 Polish cities. During a visit in a hospital outpatient clinic, pregnant women aged > 16 years fulfilled a previously validated questionnaire. The questions concerned personal data (age, parity, educational level, place of residence), toxoplasmosis knowledge (etiology, routes of transmission, symptoms, sequelae), and sources consulted to collect information. RESULTS: Overall, 465 pregnant women participated in the survey; 439 (94.4%) were aware of toxoplasmosis. Toxoplasmosis was perceived as a zoonotic disease by 77.4%, as a parasitic disease by 41.7%, as a disease transmitted through poor hand hygiene by 8.6%, as a childhood illness by 4%, and as a congenital disease by 0.4%. Regarding the transmission route, 84.5% of women pointed at a domestic cat, 46.7% at eating raw or undercooked meat. The total of 84.3% did not know toxoplasmosis symptoms, and 12.0% stated that they did not present the symptoms. In multivariate analysis, younger age (OR, 2.74; 95% CI, 1.67-4.49; p <  0.001), city residence (OR, 13.45; 95% CI, 3.12-57.89; p <  0.003), and higher education level (OR, 6.81; 95% CI, 3.69-12.59; p <  0.001) were significantly associated with better knowledge of toxoplasmosis, and the number of children (OR, 0.32; 95% CI, 0.22-0.48; p <  0.001) - with higher knowledge of the symptoms. CONCLUSIONS: Among pregnant women in Poland, the basic knowledge on toxoplasmosis is very high (94.4%). Younger age, city residence, higher education level, and the number of children turned out significantly associated with better knowledge of T. gondii and toxoplasmosis symptoms.

Is Pyroglutamic Acid a Prognostic Factor Among Patients with Suspected Infection? A Prospective Cohort Study.

Pyroglutamic acid (PGA) is a compound that accumulates during oxidative stress and hence, elevated levels may be associated with poor prognosis in patients with infection or sepsis. To examine this hypothesis, patients presenting with acute infection were recruited in the emergency department and prospectively followed for 30 days. Sport urine samples were quantified for PGA. Outcomes were mortality and composite outcome of death or organ failure. Thirty two (32%) patients had qSOFA≥2. Median urine PGA was 22.9 (IQR 17.64, 33.53) µmol/mmol creatinine. Four patients demonstrated PGA values ≥ 63 µmol/mmol creatinine. Univariate analysis showed that PGA concentration ≥ 75th percentile (i.e. 33.53 µmol/mmol creatinine) was associated with higher rates of in-hospital mortality (p = 0.041) with similar trend for PGA ≥ 63 µmol/mmol creatinine (p = 0.04). However, multivariate analysis showed that PGA was not associated with worse outcomes, whereas heart rate was associated with both composite outcomes (HR 1.0, p = 0.008 and HR 1.02, p = 0.001 for composite outcome with 30 days and in-hospital mortality, respectively). Among low risk patients, high PGA levels were consistently associated with worse outcomes. In conclusion, urine PGA concentration was not associated with worse outcomes among septic patients. Nevertheless, future studies should evaluate this association in larger cohorts.

Uninterrupted direct oral anticoagulant treatment during acute illness: Impact on clinical outcomes.

BACKGROUND: Uninterrupted drug therapy during acute illness is often associated with pharmacokinetic and pharmacodynamic variations. Among warfarin treated patients, these changes are reflected in the INR. However, in the case of direct oral anticoagulants (DOACs), given that routine laboratory monitoring is not recommended, these changes may result in unforeseen thromboembolic or bleeding events. OBJECTIVES: To determine the rate of thromboembolic (TEE) and bleeding events associated with uninterrupted DOAC compared to warfarin treatment during acute illness. METHODS: A retrospective cohort study of patients treated with DOACs or warfarin, both at steady state, who were hospitalized for acute illness. Primary outcome was any TEE or major bleeding requiring re-hospitalization within one month from discharge. Secondary outcome was a composite of major bleeding and clinically relevant non-major bleeding (CRNMB) events. RESULTS: A total of 410 patients continued oral anticoagulant treatment during their hospitalization, of whom 191 (46.6%) were on DOACs and 219 (53.4%) on warfarin, with a total of 18 (4.4%) events. Rates of TEE and major bleeding events did not differ between DOACs and warfarin treated patients (0.9% vs. 0.5% and 0.5% vs. 1%, respectively). Similarly, rate of secondary outcome was comparable between DOACs (4.7%) and warfarin (2.7%, p = 0.29). Sub-analyses demonstrated significantly higher rates among rivaroxaban (10.4%) treated patients compared to warfarin (p = 0.03). CONCLUSION: Uninterrupted treatment with DOACs during acute illness is not associated with increased risk for re-hospitalizations due to bleeding or thromboembolic events compared to warfarin. Our results suggest a higher bleeding rate among rivaroxaban treated patients at high bleeding risk.