Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial.

Remote ischaemic preconditioning reduces the risk of myocardial injury within 4 days of hip fracture surgery. We aimed to investigate the effect of remote ischaemic preconditioning on the incidence of major adverse cardiovascular events 1 year after hip fracture surgery. We performed a phase-2, multicentre, randomised, observer-blinded, clinical trial between February 2015 and September 2017. We studied patients aged ≥ 45 years with a hip fracture and a minimum of one cardiovascular risk factor. Patients were allocated randomly to remote ischaemic preconditioning applied just before surgery or no treatment (control group). Remote ischaemic preconditioning was performed on the upper arm with a tourniquet in four cycles of 5 min ischaemia and 5 min reperfusion. Primary outcome was the occurrence of major adverse cardiovascular events within 1 year of surgery. A total of 316 patients were allocated randomly to the remote ischaemic preconditioning group and 309 patients to the control group. Major adverse cardiovascular events occurred in 43 patients (13.6%) in the remote ischaemic preconditioning group compared with 51 patients (16.5%) in the control group (adjusted hazard ratio (95%CI) 0.83 (0.55-1.25); p = 0.37). Fewer patients in the remote ischaemic preconditioning group had a myocardial infarction (11 (3.5%) vs. 22 (7.1%); hazard ratio (95%CI) 0.48 (CI 0.23-1.00); p = 0.04). Remote ischaemic preconditioning did not reduce the occurrence of major adverse cardiovascular events within 1 year of hip fracture surgery. The effect of remote ischaemic preconditioning on clinical cardiovascular outcomes in non-cardiac surgery needs confirmation in appropriately powered randomised clinical trials.

Myocardial injury and mortality in patients with excessive oxygen administration before cardiac arrest.

INTRODUCTION: Hyperoxia after cardiac arrest may be associated with higher mortality, and trials have found that excess oxygen administration in patients with myocardial infarction is associated with increased infarct size. The effect of hyperoxia before cardiac arrest is sparsely investigated. Our aim was to assess the association between excessive oxygen administration before cardiac arrest and the extent of subsequent myocardial injury. METHODS: We performed a retrospective study including patients who had in-hospital cardiac arrest during 2014 in the Capital Region of Denmark. We excluded patients without peripheral oxygen saturation measurements within 48 hours before cardiac arrest. Patients were divided in three groups of pre-arrest oxygen exposure, based on average peripheral oxygen saturation and supplemental oxygen. Primary outcome was peak troponin concentration within 30 days. Secondary outcomes included 30-day mortality. Data were analyzed using multiple logistic regression and Wilcoxon rank sum test. RESULTS: Of 163 patients with cardiac arrest, 28 had excessive oxygen administration (17%), 105 had normal oxygen administration (64%) and 30 had insufficient oxygen administration (18%) before cardiac arrest. Peak troponin was median 224 ng/L in the excessive oxygen administration group vs 365 ng/L in the normal oxygen administration group (P = .54); 20 of 28 (71%) in the excessive oxygen administration group died within 30 days compared to 54 of 105 (51%) in the normal oxygen administration group. (OR 1.87, 95% CI 0.56-6.19) CONCLUSIONS: Excessive oxygen administration within 48 hours before in-hospital cardiac arrest was not statistically associated with significantly higher peak troponin or mortality.

Continuous vital sign monitoring after major abdominal surgery-Quantification of micro events.

INTRODUCTION: Millions of patients undergo major abdominal surgery worldwide each year, and the post-operative phase carries a high risk of respiratory and circulatory complications. Standard ward observation of patients includes vital sign registration at regular intervals. Patients may deteriorate between measurements, and this may be detected by continuous monitoring. The aim of this study was to compare the number of micro events detected by continuous monitoring to those documented by the widely used standardized Early Warning Score (EWS). METHODS: Fifty patients were continuously monitored with peripheral arterial oxygen saturation (SpO2 ), heart rate (HR), and respiratory rate (RR) the first 4 days after major abdominal cancer surgery. EWS was monitored as routine practice. Number and duration of events were analyzed using Fisher's exact test and Wilcoxon rank sum test. RESULTS: Continuous monitoring detected a SpO2 <92% in 98% of patients vs 16% of patients detected by EWS (P < .0001). Micro events of SpO2 <92% lasting longer than 60 minutes were found in 58% of patients by continuous monitoring vs 16% by the EWS (P < .0001). Fifty-two percent of patients had micro events of SpO2 <85% lasting longer than 10 minutes. Continuous monitoring found tachycardia in 60% of patients vs 6% by the EWS. Frequency of events for bradycardia, tachypnea, and bradypnea showed similar patterns. CONCLUSION: Very low SpO2 and tachycardia in post-operative patients are common and under-diagnosed by the EWS. Continuous monitoring can discover these micro events and potentially contribute to earlier detection and, potentially, result in prevention of clinical complications.

The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study.

BACKGROUND: Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. METHODS: We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. RESULTS: A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). CONCLUSION: Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment.

Oxygen supplementation for critically ill patients-A protocol for a systematic review.

BACKGROUND: In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients. METHODS: We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and Trial Sequential Analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Supplemental oxygen administration is widely recommended in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future trialists and decision-makers on clinical practice on supplemental oxygen administration in critically ill patients.

Perioperative hyperoxia and post-operative cardiac complications in adults undergoing non-cardiac surgery: Systematic review protocol.

BACKGROUND: Oxygen therapy is used liberally for all patients undergoing anaesthesia. Recent studies have raised concerns that it may not be without complications when arterial oxygen concentrations reach supranormal concentrations (hyperoxia). Studies of oxygen therapy have raised concerns that the risk of myocardial injury and infarction is elevated in patients with hyperoxia due to vasoconstriction and formation of reactive oxygen species. Due to lack of symptoms or silent ischaemia, post-operative myocardial injury may be missed clinically. In some studies, perioperative hyperoxia has been linked to increased long-term mortality, but cardiac complications are sparsely evaluated. The aim of this review is to summarize current evidence to assess the risk and benefits of perioperative hyperoxia on post-operative cardiac complications. METHODS: This systematic review will include meta-analyses and Trial Sequential Analyses. We will include randomized clinical trials with patients undergoing non-cardiac surgery if the allocation separates patients into a target of either higher (above 0.60) or lower (below 0.40) inspired oxygen fraction. To minimize the risk of systematic error, we will assess the risk of bias of the included trials using the Cochrane Risk of Bias Tool. The overall quality of evidence for each outcome will be assessed with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE). DISCUSSION: This systematic review will provide data on a severe, albeit rare, potential risk of oxygen therapy. We will do a trial sequential analysis to assess the robustness of results as well as help estimate the required patient size for future clinical trials.

Technological aided assessment of the acutely ill patient - The case of postoperative complications.

Surgical interventions come with complications and highly reported mortality after major surgery. The mortality may be a result of delayed detection of severe complications due to lower monitoring frequency in the general wards. Several studies have shown that continuous monitoring is superior to the manually intermittent recorded monitoring in terms of detecting abnormal physiological signs. Hopefully improved observations may result in earlier detection and clinical intervention. This narrative review will describe current monitoring possibilities for postoperative patients and how it may prevent complications. Several wireless systems are being developed for monitoring vital parameters, but many of these are not yet validated for critically ill patients. The ultimate goal with patient monitoring and detect of events is to prevent postoperative complications, death and costs in the health care system. A few studies indicate that monitoring systems detect deteriorating patients earlier than the nurses, and this was associated with less clinical instability. An important caveat of future devices is to assess their effect in relevant patient populations and not only in healthy test-subjects. Implementation of novel technologies is expensive although expected to be cost-effective if just few adverse events can be prevented. The future is here with promising devices and the possibility to give an unprecedented precise risk estimation of adverse post-surgical events. Next step is to integrate existing evidence based treatment algorithms to demonstrate the clinical efficacy of implementing the new technology.

High intraoperative inspiratory oxygen fraction and risk of major respiratory complications.

BACKGROUND: High inspiratory oxygen fraction ( FIO2 ) may improve tissue oxygenation but also impair pulmonary function. We aimed to assess whether the use of high intraoperative FIO2 increases the risk of major respiratory complications. METHODS: We studied patients undergoing non-cardiothoracic surgery involving mechanical ventilation in this hospital-based registry study. The cases were divided into five groups based on the median FIO2 between intubation and extubation. The primary outcome was a composite of major respiratory complications (re-intubation, respiratory failure, pulmonary oedema, and pneumonia) developed within 7 days after surgery. Secondary outcomes included 30-day mortality. Several predefined covariates were included in a multivariate logistic regression model. RESULTS: The primary analysis included 73 922 cases, of whom 3035 (4.1%) developed a major respiratory complication within 7 days of surgery. For patients in the high- and low-oxygen groups, the median FIO2 was 0.79 [range 0.64-1.00] and 0.31 [0.16-0.34], respectively. Multivariate logistic regression analysis revealed that the median FIO2 was associated in a dose-dependent manner with increased risk of respiratory complications (adjusted odds ratio for high vs low FIO2 1.99, 95% confidence interval [1.72-2.31], P -value for trend <0.001). This finding was robust in a series of sensitivity analyses including adjustment for intraoperative oxygenation. High median FIO2 was also associated with 30-day mortality (odds ratio for high vs low FIO2 1.97, 95% confidence interval [1.30-2.99], P -value for trend <0.001). CONCLUSIONS: In this analysis of administrative data on file, high intraoperative FIO2 was associated in a dose-dependent manner with major respiratory complications and with 30-day mortality. The effect remained stable in a sensitivity analysis controlled for oxygenation. CLINICAL TRIAL REGISTRATION: NCT02399878.

Neuraxial block and postoperative epidural analgesia: effects on outcomes in the POISE-2 trial†.

BACKGROUND: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. METHODS: 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores. RESULTS: Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74-1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89-2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09). CONCLUSIONS: Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects.

Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock.

BACKGROUND: Supplemental oxygen therapy is used for intensive care (ICU) patients with severe sepsis, but with no general guidelines and few safety data. The aim of this observational study was to describe the variability in oxygen administration as well as the association between partial pressure of arterial oxygen (PaO2 ) and mortality. METHODS: We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2 ) from trial inclusion and the following 5 days, and assessed the association between PaO2 and 90-day mortality. RESULTS: The median PaO2 was 9.8 kPa [5-95% range 6.4-19.9] and FiO2 was 0.51 [5-95% range 0.27-1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19-1.65] in patients with average PaO2 < 8 kPa and 1.29 [95% CI: 0.84-1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10-12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17-1.58] in patients with an average FiO2 0.60-0.80 and 2.10 [95% CI: 1.88-2.23] in patients with an average FiO2  ≥ 0.80 as compared to patients with an average FiO2  ≤ 0.40. CONCLUSION: Administration of oxygen in patients with severe sepsis resulted in a wide range of PaO2 . Significantly higher mortality was observed in patients with an average PaO2 < 8 kPa and FiO2 ≥ 0.60. The results do not imply causation and the associations between average PaO2 and adverse outcomes have to be assessed further.

Risk of new or recurrent cancer after a high perioperative inspiratory oxygen fraction during abdominal surgery.

BACKGROUND: Administration of supplemental oxygen in the perioperative period is controversial, as it may increase long-term mortality. Our aim was to assess the association between 80% oxygen and occurrence of subsequent cancer in patients undergoing abdominal surgery in a post hoc analysis of the PROXI trial. METHODS: The 1386 patients in the PROXI trial underwent elective or emergency laparotomy between 2006 and 2008 with randomization to either 80% or 30% oxygen during and for 2 h after surgery. We retrieved follow-up status regarding vital status, new cancer diagnoses, and new histological cancer specimens. Data were analysed using the Cox proportional hazards model. RESULTS: Follow-up was complete in 1377 patients (99%) after a median of 3.9 yr. The primary outcome of new cancer diagnosis or new malignant histological specimen occurred in 140 of 678 patients (21%) in the 80% oxygen group vs 150 of 699 patients (21%) assigned to 30% oxygen; hazards ratio 1.06 [95% confidence interval (CI) 0.84, 1.34], P=0.62. Cancer-free survival was significantly shorter in the 80% oxygen group; hazards ratio 1.19 (95% CI 1.01, 1.42), P=0.04, as was the time between surgery and new cancer, median 335 vs. 434 days in the 30% oxygen group. In patients with localized disease, non-significant differences in cancer and cancer-free survival were found with hazard ratios of 1.31 and 1.29, respectively. CONCLUSIONS: Although new cancers occurred at similar rate, the cancer-free survival was significantly shorter in the 80% oxygen group, but this did not appear to explain the excess mortality in the 80% oxygen group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01723280).

Transfusion practice and complications after laparotomy--an observational analysis of a randomized clinical trial.

BACKGROUND: Transfusion of allogeneic red blood cells (RBC) may be associated with side effects. This study aimed to assess whether an association could be detected between transfusion practice and the occurrence of complications after laparotomy. STUDY DESIGN AND METHODS: This study is an observational analysis of data from a randomized trial in 1400 patients who underwent laparotomy. A subgroup of 224 transfused patients with an intraoperative blood loss ≥200 ml were included in the analysis. Logistic regression analysis was used to investigate risk factors for postoperative complications. The ratio of intraoperative RBC transfusion to blood loss was computed, and patients grouped by the median into a liberal transfusion practice (ratio equal to or above the median) and a restrictive transfusion practice group (ratio below the median). RESULTS: Surgical site infection occurred in 27% of patients in the liberal group vs. 20% of patients in the restrictive group with an OR of 1·5 [95% CI: 0·8-2·9] (P=0·18) and an OR of 1·2 [95% CI: 0·5-2·9] (P=0·73) when adjusting for known confounding variables. Pneumonia occurred in 14% vs. 8% in the liberal and restrictive group, respectively (adjusted P=0·07), and admission to the intensive care unit was 15% vs. 7%, respectively (adjusted P=0·02), but no other significant differences were found. CONCLUSION: A liberal transfusion practice was not significantly associated with postoperative complications, but pneumonia tended to be more common in the liberal group, which was more often admitted to the intensive care unit.

Post-operative pain treatment in Denmark from 2000 to 2009: a nationwide sequential survey on organizational aspects.

BACKGROUND: In Denmark, the first acute pain service (APS) was introduced in 1993. An important objective became to facilitate implementation of accelerated post-operative rehabilitation programmes (ACC) in selected procedures in abdominal, gynaecological and orthopaedic surgery. Therefore, it is of considerable interest to study the association between the developments of post-operative pain management and the ACC by sequential analyses from 2000 to 2009. METHODS: In 2000, 2003, 2006 and 2009, a questionnaire was mailed to all Danish anaesthesiology departments. The headings of the questionnaire were demographics of responder departments, resources allocated to pain management methods, quality assessment methods, research activities and implementation of ACC. RESULTS: The responder rates varied between 80% and 94% (mean 88%) representing a mean number of anaesthetics of 340.000 per year. The number of APSs in the study period varied in university hospitals between 52% and 71% (P = 0.01), regional hospitals between 8% and 40% (P < 0.01), and local hospitals between 0% and 47% (P < 0.01). The prevalences of departments actively engaged in ACC were 40% in 2000, 54% in 2003, 73% in 2006 and 80% in 2009 (P < 0.01). CONCLUSIONS: The study, spanning nearly a decade, illustrates that following an increase in number of APSs from 2000 to 2006, followed by a significant decline, a steadily increasing number of departments implemented ACC.

Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention.

Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant (CRSSI) and whether there is agreement between evaluations according to the CDC criteria, the ASEPSIS score (Additional treatment, presence of Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of Stay) and CRSSI. We included 54 patients diagnosed with SSI and a matched control group (N=46) without SSI according to the CDC criteria after laparotomy. Two blinded experienced surgeons evaluated the hospital records and determined whether patients had CRSSI, based on the following criteria: antibiotic treatment, surgical intervention, prolonged hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant. There was substantial agreement between the CDC criteria and CRSSI [kappa=0.69; 95% confidence interval (CI): 0.55-0.83] and fair agreement between the ASEPSIS score and the CDC criteria (kappa=0.23; 95% CI: 0-0.49) and between the ASEPSIS score and CRSSI (kappa=0.39; 95% CI: 0.17-0.61). The CDC criteria represent a suitable standard definition for monitoring and identifying SSI, even if some cases of less clinically significant superficial SSI are included.

Depth of anaesthesia monitoring in obese patients: a randomized study of propofol-remifentanil.

BACKGROUND: In obese patients, depth of anaesthesia monitoring could be useful in titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia monitoring would reduce recovery time and use of anaesthetics in obese patients receiving propofol and remifentanil. METHODS: We investigated 38 patients with a body mass index >or=30 kg/m(2) scheduled for an abdominal hysterectomy. Patients were randomized to either titration of propofol and remifentanil according to a cerebral state monitor (CSM group) or according to usual clinical criteria (control group). The primary end point was time to eye opening and this was assessed by a blinded observer. RESULTS: Time to eye opening was 11.8 min in the CSM group vs. 13.4 min in the control group (P=0.58). The average infusion rate for propofol was a median of 516 vs. 617 mg/h (P=0.24) and for remifentanil 2393 vs. 2708 microg/h (P=0.04). During surgery, when the cerebral state index was continuously between 40 and 60, the corresponding optimal propofol infusion rate was 10 mg/kg/h based on ideal body weight. CONCLUSION: No significant reduction in time to eye opening could be demonstrated when a CSM was used to titrate propofol and remifentanil in obese patients undergoing a hysterectomy. A significant reduction in remifentanil consumption was found.

Biphasic cardiac output changes during onset of spinal anaesthesia in elderly patients.

BACKGROUND AND OBJECTIVE: In most studies of cardiac output changes after spinal anaesthesia, the time-resolution is limited. The aim of this study was to demonstrate cardiac output changes with high time-resolution during onset of spinal anaesthesia in elderly patients. METHODS: We investigated 32 patients aged 60 yr scheduled for elective lower limb surgery. Fourteen received concurrent cardiovascular medication. Cardiac output was measured every 10 s using a pulse wave algorithm derived from the radial artery pressure curve, after calibration with lithium chloride (LiDCOplus). Data collection ended when the patients were ready for surgery, or if ephedrine was given to raise the mean arterial pressure. RESULTS: Cardiac output increased initially reaching a maximum after a mean of 7 min. The average increase was 1.1 L min(-1) (P<0.0001). This occurred when mean arterial pressure was reduced 14 mmHg on average. At the end of data collection, cardiac output decreased 0.5 L min(-1) from baseline (P=0.02). Mean arterial pressure decreased progressively in all patients, and only minimal changes in heart rate were found. CONCLUSIONS: Using this high time-resolution method, we detected biphasic changes in cardiac output during onset of spinal anaesthesia. Initially, cardiac output increased. Subsequently, it was significantly reduced from baseline, although this decrease was of minor clinical importance.