Karim S. Ladha

Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study

Objective To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Design Hospital based registry study. Setting Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. Participants 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Interventions Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. Main outcome measure Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Results Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. Conclusions Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.

Dose-dependent Association between Intermediate-acting Neuromuscular-blocking Agents and Postoperative Respiratory Complications

Background:Duration of action increases with repeated administration of neuromuscular-blocking agents, and intraoperative use of high doses of neuromuscular-blocking agent may affect respiratory safety. Methods:In a hospital-based registry study on 48,499 patients who received intermediate-acting neuromuscular-blocking agents, the authors tested the primary hypothesis that neuromuscular-blocking agents are dose dependently associated with the risk of postoperative respiratory complications. In the secondary analysis, the authors evaluated the association between neostigmine dose given for reversal of neuromuscular-blocking agents and respiratory complications. Post hoc, the authors evaluated the effects of appropriate neostigmine reversal (neostigmine ⩽60 &mgr;g/kg after recovery of train-of-four count of 2) on respiratory complications. The authors controlled for patient-, anesthesia-, and surgical complexity–related risk factors. Results:High doses of neuromuscular-blocking agents were associated with an increased risk of postoperative respiratory complications (n = 644) compared with low doses (n = 205) (odds ratio [OR], 1.28; 95% CI, 1.04 to 1.57). Neostigmine was associated with a dose-dependent increase in the risk of postoperative respiratory complications (OR, 1.51; 95% CI, 1.25 to 1.83). Post hoc analysis revealed that appropriate neostigmine reversal eliminated the dose-dependent association between neuromuscular-blocking agents and respiratory complications (for neuromuscular-blocking agent effects with appropriate reversal: OR, 0.98; 95% CI, 0.63 to 1.52). Conclusions:The use of neuromuscular-blocking agents was dose dependently associated with increased risk of postoperative respiratory complications. Neostigmine reversal was also associated with a dose-dependent increase in the risk of respiratory complications. However, the exploratory data analysis suggests that the proper use of neostigmine guided by neuromuscular transmission monitoring results can help eliminate postoperative respiratory complications associated with the use of neuromuscular-blocking agents.

Variations in the Use of Perioperative Multimodal Analgesic Therapy

Background:Practice guidelines for perioperative pain management recommend that multimodal analgesic therapy should be used for all postsurgical patients. However, the proportion of patients who actually receive this evidence-based approach is unknown. The objective of this study was to describe hospital-level patterns in the utilization of perioperative multimodal analgesia. Methods:Data for the study were obtained from the Premier Research Database. Patients undergoing below-knee amputation, open lobectomy, total knee arthroplasty, and open colectomy between 2007 and 2014 were included in the analysis. Patients were considered to have multimodal therapy if they received one or more nonopioid analgesic therapies. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of multimodal therapy use while adjusting for the case mix of patients and hospital characteristics and accounting for random variation. Results:The cohort consisted of 799,449 patients who underwent a procedure at 1 of 315 hospitals. The mean probability of receiving multimodal therapy was 90.4%, with 95% of the hospitals having a predicted probability between 42.6 and 99.2%. A secondary analysis examined whether patients received two or more nonopioid analgesics, which gave an average predicted probability of 54.2%, with 95% of the hospitals having a predicted probability between 9.3 and 93.2%. Conclusions:In this large nationwide sample of surgical admissions in the United States, the authors observed tremendous variation in the utilization of multimodal therapy not accounted for by patient or hospital characteristics. Efforts should be made to identify why there are variations in the use of multimodal analgesic therapy and to promote its adoption in appropriate patients.

Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy.

Objectives: In this study, we examined whether (1) positive end-expiratory pressure (PEEP) has a protective effect on the risk of major postoperative respiratory complications in a cohort of patients undergoing major abdominal surgeries and craniotomies, and (2) the effect of PEEP is differed by surgery type. Background: Protective mechanical ventilation with lower tidal volumes and PEEP reduces compounded postoperative complications after abdominal surgery. However, data regarding the use of intraoperative PEEP is conflicting. Methods: In this observational study, we included 5915 major abdominal surgery patients and 5063 craniotomy patients. Analysis was performed using multivariable logistic regression. The primary outcome was a composite of major postoperative respiratory complications (respiratory failure, reintubation, pulmonary edema, and pneumonia) within 3 days of surgery. Results: Within the entire study population (major abdominal surgeries and craniotomies), we found an association between application of PEEP ≥5 cmH2O and a decreased risk of postoperative respiratory complications compared with PEEP <5 cmH2O. Application of PEEP >5 cmH2O was associated with a significant lower odds of respiratory complications in patients undergoing major abdominal surgery (odds ratio 0.53, 95% confidence interval 0.39 – 0.72), effects that translated to deceased hospital length of stay [median hospital length of stay : 6 days (4–9 days), incidence rate ratios for each additional day: 0.91 (0.84 – 0.98)], whereas PEEP >5 cmH2O was not significantly associated with reduced odds of respiratory complications or hospital length of stay in patients undergoing craniotomy. Conclusions: The protective effects of PEEP are procedure specific with meaningful effects observed in patients undergoing major abdominal surgery. Our data suggest that default mechanical ventilator settings should include PEEP of 5–10 cmH2O during major abdominal surgery.

The Deyo-Charlson and Elixhauser-van Walraven Comorbidity Indices as predictors of mortality in critically ill patients

Objectives Our primary objective was to compare the utility of the Deyo-Charlson Comorbidity Index (DCCI) and Elixhauser-van Walraven Comorbidity Index (EVCI) to predict mortality in intensive care unit (ICU) patients. Setting Observational study of 2 tertiary academic centres located in Boston, Massachusetts. Participants The study cohort consisted of 59 816 patients from admitted to 12 ICUs between January 2007 and December 2012. Primary and secondary outcome For the primary analysis, receiver operator characteristic curves were constructed for mortality at 30, 90, 180, and 365 days using the DCCI as well as EVCI, and the areas under the curve (AUCs) were compared. Subgroup analyses were performed within different types of ICUs. Logistic regression was used to add age, race and sex into the model to determine if there was any improvement in discrimination. Results At 30 days, the AUC for DCCI versus EVCI was 0.65 (95% CI 0.65 to 0.67) vs 0.66 (95% CI 0.65 to 0.66), p=0.02. Discrimination improved at 365 days for both indices (AUC for DCCI 0.72 (95% CI 0.71 to 0.72) vs AUC for EVCI 0.72 (95% CI 0.72 to 0.72), p=0.46). The DCCI and EVCI performed similarly across ICUs at all time points, with the exception of the neurosciences ICU, where the DCCI was superior to EVCI at all time points (1-year mortality: AUC 0.73 (95% CI 0.72 to 0.74) vs 0.68 (95% CI 0.67 to 0.70), p=0.005). The addition of basic demographic information did not change the results at any of the assessed time points. Conclusions The DCCI and EVCI were comparable at predicting mortality in critically ill patients. The predictive ability of both indices increased when assessing long-term outcomes. Addition of demographic data to both indices did not affect the predictive utility of these indices. Further studies are needed to validate our findings and to determine the utility of these indices in clinical practice.

Predictors of In-hospital Postoperative Opioid Overdose After Major Elective Operations: A Nationally Representative Cohort Study

Objective: The aim of this study was to describe national trends and outcomes of in-hospital postoperative opioid overdose (OD) and identify predictors of postoperative OD. Summary of Background Data: In 2000, the Joint Commission recommended making pain the 5th vital sign, increasing the focus on postoperative pain control. However, the benefits of pain management must be weighed against the potentially lethal risk of opioid OD. Methods: This is a retrospective multi-institutional cohort study of patients undergoing 1 of 6 major elective inpatient operation from 2002 to 2011 using the Nationwide Inpatient Sample, an approximately 20% representative sample of all United States hospital admissions. Patients with postoperative OD were identified using ICD-9 codes for poisoning from opioids or adverse effects from opioids. Multivariate logistic regression was used to identify independent predictors. Results: Among 11,317,958 patients, 9458 (0.1%) had a postoperative OD; this frequency doubled over the study period from 0.6 to 1.1 overdoses per 1000 cases. Patients with postoperative OD died more frequently during their hospitalization (1.7% vs 0.4%, P < 0.001). Substance abuse history was the strongest predictor of OD (odds ratio = 14.8; 95% confidence interval: 12.7–17.2). Gender, age, income, geographic location, operation type, and certain comorbid diseases also predicted OD (P < 0.05). Hospital variables, including teaching status, size, and urban/rural location, did not predict postoperative OD. Conclusions: Postoperative OD is a rare, but potentially lethal complication, with increasing incidence. Postoperative monitoring and treatment safety interventions should be thoughtfully employed to target high-risk patients and avoid this potentially fatal complication.

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.

Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials.

Background:N-methyl-D-aspartate receptor antagonists have been shown to reduce perioperative pain and opioid use. The authors performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. Methods:PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Pubget, and EMBASE were searched. Studies were included if they were randomized, double-blinded, placebo-controlled trials written in English, and performed on patients 12 yr or older. For comparison of opioid use, included studies tracked total consumption of IV or intramuscular opioids over 24 to 48 h. Pain score comparisons were performed at 1, 4 to 6, and 24 h postoperatively. Difference in means (MD) was used for effect size. Results:Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD, −10.51 mg IV morphine equivalents; 95% CI, −16.48 to −4.53 mg; P = 0.0006). In 884 patients from 13 trials, pain at 1 h favored dextromethorphan (MD, −1.60; 95% CI, −1.89 to −1.31; P < 0.00001). In 950 patients from 13 trials, pain at 4 to 6 h favored dextromethorphan (MD, −0.89; 95% CI, −1.11 to −0.66; P < 0.00001). In 797 patients from 12 trials, pain at 24 h favored dextromethorphan (MD, −0.92; 95% CI, −1.24 to −0.60; P < 0.00001). Conclusion:This meta-analysis suggests that dextromethorphan use perioperatively reduces the postoperative opioid consumption at 24 to 48 h and pain scores at 1, 4 to 6, and 24 h.

Impact of Perioperative Epidural Placement on Postdischarge Opioid Use in Patients Undergoing Abdominal Surgery.

Background:Opioids play a crucial role in providing analgesia throughout the perioperative period; however, patients may become persistent users of these medications months after surgery. Epidurals have been posited to prevent the development of persistent pain, but there are little data on the effect of epidurals on persistent opioid use. Methods:This study was conducted using a claims database of a large, nationwide commercial health insurer. Opioid-naive patients who underwent open abdominal surgery from January 2004 to December 2013 were included in the study. Propensity scores for epidural placement were calculated accounting for demographic characteristics, resource utilization, and comorbid conditions (including medical, psychiatric, and pain conditions). Time-to-event analysis was used with the primary outcome defined as 30 days without filling an opioid prescription after discharge. In addition, total morphine equivalents dispensed within 90 days of discharge were also calculated for each patient. Results:A total of 6,432 patients were included in the final propensity score–matched cohort. The Cox proportional hazards ratio was 0.96 (95% CI, 0.91 to 1.01; P = 0.0910) for the relation between epidural placement and time till a 30-day gap without filling an opioid prescription. There was no difference in the total morphine equivalents dispensed within 90 days of discharge between the groups (P = 0.7670). Conclusions:Epidural placement was not protective against persistent opioid use in a large cohort of opioid-naive patients undergoing abdominal surgery. This finding does not detract from the other potential benefits of epidural placement. More research is needed to understand the mechanism of persistent opioid use after surgery and its prevention.

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

We thought that the rate of postoperative pulmonary complications might be higher after pressure‐controlled ventilation than after volume‐controlled ventilation. We analysed peri‐operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure‐controlled ventilation, odds ratio (95%CI) 1.29 (1.21–1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure‐controlled ventilation compared with volume‐controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg−1 vs. 1.23 (1.11) ml.kg−1, p < 0.001; and 3.91 (3.47) cmH2O vs. 3.40 (2.69) cmH2O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure‐controlled ventilation compared with volume‐controlled ventilation at positive end‐expiratory pressures < 5 cmH2O was 1.40 (1.26–1.55) and 1.20 (1.11–1.31) when ≥ 5 cmH2O, both p < 0.001, a relative risk ratio of 1.17 (1.03–1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure‐controlled ventilation compared with volume‐controlled ventilation at driving pressures of < 19 cmH2O was 1.37 (1.27–1.48), p < 0.001, and 1.16 (1.04–1.30) when ≥ 19 cmH2O, p = 0.011, a relative risk ratio of 1.18 (1.07–1.30), p = 0.016. Our data support volume‐controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.