Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a ...diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19.
This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied.
1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 14.6-24.0 J/min in patients with and 13.2 10.2-18.0 J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (OR
1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRR
0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3).
A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.
Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are ...associated with delirium after surgery.
Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery.
Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio ORadj=1.71; 95% confidence interval CI, 1.40–2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30–2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02–1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00–1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90–1.71; P=0.181).
Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that ...intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium.
A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied.
Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each μg/kg increase in the cumulative phenylephrine dose).
The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.
Patients suffering from obstructive sleep apnea (OSA) experience chronic sleep disturbances and desaturation, factors that have been associated with postoperative delirium and that can be aggravated ...after anesthesia for complex procedures. We investigated whether OSA is associated with delirium after anesthesia, and whether this association is modified by procedural complexity.
Hospitalized patients ≥60 years who underwent general anesthesia or procedural sedation for procedures of moderate-to-high complexity between 2009 and 2020 at a tertiary health care network in Massachusetts were included. The primary exposure was OSA, defined based on International Classification of Diseases ( Ninth/Tenth Revision, Clinical Modification ) ( ICD-9 / 10-CM ) diagnostic codes, structured nursing interviews, anesthesia alert notes, and a validated risk score (BOSTN body mass index, observed apnea, snoring, tiredness, and neck circumference). The primary end point was delirium within 7 days after the procedure. Multivariable logistic regression and effect modification analyses adjusted for patient demographics, comorbidities, and procedural factors were applied.
A total of 46,352 patients were included, of which 1694 patients (3.7%) developed delirium, 537 (3.2%) with OSA, and 1,157 (4.0%) without OSA. In adjusted analyses, OSA was not associated with postprocedural delirium in the overall cohort (adjusted odds ratio OR adj , 1.06; 95% confidence interval CI, 0.94-1.20; P = .35). However, a high procedural complexity modified the primary association ( P value for interaction = .002). OSA patients had a higher risk of delirium after high-complexity procedures (≥40 work relative value units) such as cardiac (OR adj , 1.33; 95% CI, 1.08-1.64; P = .007, P value for interaction = .005) or thoracic surgery (OR adj , 1.89; 95% CI, 1.19-3.00; P = .007, P value for interaction = .009), but no increased risk after moderate complexity procedures, including general surgery (OR adj , 0.86; 95% CI, 0.55-1.35; P = .52).
Compared to non-OSA patients, a history of OSA is associated with a higher risk after high-complexity procedures such as cardiac or thoracic surgery but not after procedures of moderate complexity.
The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative ...respiratory complications is dependent on respiratory system elastance.
We retrospectively recorded tidal volume (Vt; ml kg−1 ideal body weight IBW) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/ml kg−1). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low Vt ≤8 ml kg−1 or high Vt >8 ml kg−1), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling.
Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg−1; 95% confidence interval CI, 1.35–1.50; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O−1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% 95% CI, 0.0–0.5 at 41.2 ml cm H2O−1 compliance, compared with 5.8% 95% CI, 3.8–7.8 at 14 ml cm H2O−1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O−1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001).
The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We examined the effects of dexamethasone on postoperative mortality, recurrence-free survival, and side effects in patients undergoing oncologic operations.
Dexamethasone prevents nausea and vomiting ...after anesthesia and may affect cancer proliferation.
A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included. Multivariable logistic regression was applied to investigate the effect of dexamethasone on 1-year mortality and recurrence-free survival. Effect modification by the cancer's potential for immunogenicity, defined as a recommendation for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines, was investigated through interaction term analysis. Key safety endpoints were dexamethasone-associated risk of hyperglycemia >180 mg/dL within 24 hours and surgical site infections within 30 days after surgery.
Dexamethasone was administered to 38.2% (11,666/30,561) of patients (6.5±2.3 mg). Overall, 3.2% (n=980/30,561) died and 15.4% (n=4718/30,561) experienced cancer recurrence within 1 year of the operation. Dexamethasone was associated with a -0.6% (95% confidence interval: -1.1, -0.2, P =0.007) 1-year mortality risk reduction adjusted odds ratio (OR adj ): 0.79 (0.67, 0.94), P =0.009; hazard ratio=0.82 (0.69, 0.96), P =0.016 and higher odds of recurrence-free survival OR adj : 1.28 (1.18, 1.39), P <0.001. This effect was only present in patients with solid cancers who were defined as not to respond to checkpoint inhibitor therapy OR adj : 0.70 (0.57, 0.87), P =0.001 vs OR adj : 1.13 (0.85, 1.50), P =0.40. A high (>0.09 mg/kg) dose of dexamethasone increased the risk of postoperative hyperglycemia OR adj : 1.55 (1.32, 1.82), P <0.001, but not for surgical site infections OR adj : 0.84 (0.42, 1.71), P =0.63.
Dexamethasone is associated with decreased 1-year mortality and cancer recurrence in patients undergoing surgical resection of cancers that are not candidates for immune modulators. Dexamethasone increased the risk of postoperative hyperglycemia, however, no increase in surgical site infections was identified.
Sugammadex reversal of neuromuscular block facilitates recovery of neuromuscular function after surgery, but the drug is expensive. We evaluated the effects of sugammadex on hospital costs of care.
...We analysed 79 474 adult surgical patients who received neuromuscular blocking agents and reversal from two academic healthcare networks between 2016 and 2021 to calculate differences in direct costs. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP–NIS) to calculate differences in total costs in US dollars. Perioperative risk profiles were defined based on ASA physical status and admission status (ambulatory surgery vs hospitalisation).
Based on our registry data analysis, administration of sugammadex vs neostigmine was associated with lower direct costs (–1.3% lower costs; 95% confidence interval CI, –0.5 to –2.2%; P=0.002). In the HCUP-NIS matched cohort, sugammadex use was associated with US$232 lower total costs (95% CI, –US$376 to –US$88; P=0.002). Subgroup analysis revealed that sugammadex was associated with US$1042 lower total costs (95% CI, –US$1198 to –US$884; P<0.001) in patients with lower risk. In contrast, sugammadex was associated with US$620 higher total costs (95% CI, US$377 to US$865; P<0.001) in patients with a higher risk (American Society of Anesthesiologists physical status ≥3 and preoperative hospitalisation).
The effects of using sugammadex on costs of care depend on patient risk, defined based on comorbidities and admission status. We observed lower costs of care in patients with lower risk and higher costs of care in hospitalised surgical patients with severe comorbidities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ...ambulatory surgery.
We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs.
Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: –9.5 min; 95% confidence interval 95% CI, –10.5 to –8.5 min; adjusted difference in direct hospital costs: –US$77; 95% CI, –$88 to –$66; respectively; P<0.001). The association was magnified in patients over age 65 yr, with ASA physical status >2 undergoing short procedures (<2 h) (adjusted difference in PLOS-ACF: –18.2 min; 95% CI, –23.8 to –12.4 min; adjusted difference in direct hospital costs: –$176; 95% CI, –$220 to –$128; P<0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P<0.001), which mediated its effects on length of stay.
Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
