Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

Hospital infections and health-related quality of life after cardiac surgery: a multicenter survey.

BACKGROUND: Recent research suggested that hospital infections are a predictive marker for physical non-recovery one year after cardiothoracic surgery. The purpose of this study was to explore whether this risk factor is etiologic. Additional, the influence of a potential effect modifying factor, diabetes mellitus, was investigated. METHODS: In this multicenter study, patients underwent elective or urgent cardiothoracic surgery between 01-01-2015 and 31-12-2019, and completed pre- and one year post-operative Short Form Health Survey 36/12 quality of life questionnaires. A binary logistic regression model, in which the inverse of the propensity score for infection risk was included as a weight variable, was used. Second, this analysis was stratified for diabetes mellitus status. RESULTS: 8577 patients were included. After weighing for the propensity score, the standardized mean differences of all variables decreased and indicated sufficient balance between the infection and non-infection groups. Hospital infections were found to be a risk factor for non-recovery after cardiothoracic surgery in the original and imputed dataset before weighting. However, after propensity score weighing, hospital infections did not remain significantly associated with recovery (OR for recovery = 0.79; 95% CI [0.60-1.03]; p = 0.077). No significant interaction between diabetes mellitus and hospital infections on recovery was found (p = 0.845). CONCLUSIONS: This study could not convincingly establish hospital infections as an etiologic risk factor for non-improvement of physical recovery in patients who underwent cardiothoracic surgery. In addition, there was no differential effect of hospital infections on non-improvement of physical recovery for patients with and without diabetes mellitus. Trial registration International Clinical Trials Registry Platform ID NL9818; date of registration, 22-10-2021 ( https://trialsearch.who.int/ ).

Ten-year outcome of laparoscopic and conventional nissen fundoplication: randomized clinical trial.

OBJECTIVE: To compare 10 years outcome of a multicenter randomized controlled trial on laparoscopic (LNF) and conventional Nissen fundoplication (CNF), with focus on effectiveness and reoperation rate. SUMMARY OF BACKGROUND DATA: LNF has replaced CNF as surgical treatment for gastroesophageal reflux disease (GERD). Decisions are based on equal short-term effectiveness and reduced morbidity, but confirmation by long-term level 1 evidence is lacking. METHODS: From 1997 to 1999, 177 proton pump inhibitor (PPI)-refractory GERD patients were randomized to undergo LNF or CNF. The 10 years results of surgery on reflux symptoms, general health, PPI use, and reoperation rates, are described. High-resolution manometry, 24-hour pH-impedance monitoring and barium swallow were performed in symptomatic patients only. RESULTS: A total of 148 patients (79 LNF, 69 CNF) participated in this 10-year follow-up study. GERD symptoms were relieved in 92.4% and 90.7% (NS) after LNF and CNF, respectively. Severity of heartburn and dysphagia were similar, but slightly more patients had relief of regurgitation after LNF (98.7% vs. 91.0%; P = 0.030). The percentage of patients using PPIs slowly increased with time in both groups to 26.6% for LNF and 22.4% for CNF (NS). General health (74.7% vs. 72.7%; NS) and quality of life (visual analogue scale score: 65.3 vs. 61.4; NS) improved similarly in both groups. The percentage of patients who would have opted for surgery again was similar as well (78.5% vs. 72.7%; NS). Twice as many patients underwent reoperation after CNF compared with LNF (12 [15.2%] vs. 24 [34.8%]; P = 0.006), including a higher number of incisional hernia corrections (2 vs. 9; P = 0.015). Mean interval between operation and reintervention was longer after CNF (22.9 vs. 50.6 months; P = 0.047). Of the patients who were dependent on daily PPI therapy at 10 years (LNF 10, CNF 10), 7 patients (LNF 3, CNF 4) had recurrent GERD on pH-impedance monitoring, 5 of them with some form of anatomic recurrence. A total of 13 of 20 (65.0%) patients did not have recurrent GERD. Fourteen patients had an abnormal high-resolution manometry. CONCLUSIONS: CNF carries a higher risk for surgical reintervention compared with LNF, mainly due to incisional hernia corrections. The 10-year effectiveness of LNF and CNF is comparable in terms of improvement of GERD symptoms, PPI use, quality of life, and objective reflux control. Consequently, the long-term results from this trial lend level 1 support to the use of LNF as the surgical procedure of choice for GERD.

The Visick score: a good measure for the overall effect of antireflux surgery?

OBJECTIVE: In scoring the outcome of antireflux surgery, it is extremely difficult to combine the effect on reflux symptoms and esophageal acid exposure in one and the same single system - the Visick score revisited. The aim of this study was to correlate subjective outcome variables and objective outcome variables in an attempt to come to an overall reproducible scoring system. MATERIAL AND METHODS: From 1997 to 1999, a randomized trial was set up to compare 98 patients who had undergone laparoscopic Nissen fundoplication (LNF) with 79 patients treated with conventional Nissen fundoplication (CNF). All patients were requested to complete a questionnaire, before and 3, 6, 12, 24 and 60 months after surgery. A subgroup of 87 patients agreed to undergo objective evaluation by pH-metry. The results of all these assessments were correlated with the effect of surgery on the Visick score. RESULTS: After LNF and CNF, 79 and 69 patients, respectively, completed the questionnaires. After 5 years, complaints about heartburn, regurgitation and dysphagia were still significantly improved in the majority of patients, but in these groups, 6, 3 and 27% of patients, respectively, experienced deterioration. Visick score I or II (complaints resolved or improved) was recorded by 87% of patients. The Visick score correlated with the reduction of postoperative reflux symptom grades for heartburn, but not with the reduction of regurgitation, dysphagia and esophageal acid exposure. CONCLUSIONS: Although this study shows that the Visick score can be applied to monitor the subjective effect of primary antireflux surgery as it correlates well with the most prominent symptom of GERD (heartburn), it also underlines the difficulty in adequately scoring symptomatic outcome of antireflux surgery.

Impact of surgeon experience on 5-year outcome of laparoscopic Nissen fundoplication.

OBJECTIVE: To investigate the 5-year effect of surgeon experience with laparoscopic Nissen fundoplication (LNF). In 2000, a randomized controlled trial (RCT) was prematurely terminated because LNF for gastroesophageal reflux disease was associated with a higher risk to develop dysphagia than conventional Nissen fundoplication (CNF). Criticism focused on alleged bias caused by the relative lack of experience with the laparoscopic approach of the participating surgeons. DESIGN: Multicenter RCT and prospective cohort study. SETTING: University medical centers and tertiary teaching hospitals. PATIENTS: In the RCT, 74 patients underwent CNF and 93 patients underwent LNF (LNFI). The complete setup of the cohort study (LNFII) (n = 121) mirrored the RCT, except that surgeon experience increased from more than 5 to more than 30 LNFs per surgeon. INTERVENTIONS: Conventional Nissen fundoplication, LNFI, and LNFII. MAIN OUTCOME MEASURES: Intraoperative and in-hospital characteristics, objective reflux control, and clinical outcome. RESULTS: In LNFII, operating time (110 vs 165 minutes; P < .001), dysphagia (2.5% vs 12.3%; P = .008), dilatations for dysphagia (0.8% vs 7.0%; P = .02), and conversions (3.5% vs 7.7%; P = .19) were reduced compared with LNFI. Moreover, in LNFII, hospitalization (4.2 vs 5.6 days; P = .07 and 4.2 vs 7.6 days; P < .001) and in-hospital complications (5.1% vs 13.5%; P = .046 and 5.1% vs 19.3%; P = .005) were reduced compared with LNFI and CNF, respectively. In LNFII, the 6-month reintervention rate was reduced compared with LNFI (0.8% vs 10.1%; P = .002). Esophagitis and esophageal acid exposure at 3 months and reflux symptoms, proton-pump inhibitor use, and quality of life at 5 years improved similarly. CONCLUSIONS: Operating time, complications, hospitalization, early dysphagia, dilatations for dysphagia, and reintervention rate after LNF improve significantly when surgeon experience increases from more than 5 to more than 30 LNFs. In contrast, short-term objective reflux control and 5-year clinical outcome do not improve with experience. In experienced hands, LNF reduces in-hospital complications and hospitalization compared with CNF, with similar 5-year effectiveness and reoperation rate.

Five-year subjective and objective results of laparoscopic and conventional Nissen fundoplication: a randomized trial.

OBJECTIVE: The purpose of this prospective study was to compare the subjective and objective outcome of laparoscopic (LNF) and conventional Nissen fundoplication (CNF) up to 5 years after surgery as obtained in a multicenter randomized controlled trial. SUMMARY OF BACKGROUND DATA: LNF is regarded as surgical treatment of first choice for refractory gastroesophageal reflux disease by many surgeons based on several short- and mid-term studies. The long-term efficacy of Nissen fundoplication, however, is still questioned as objective data gathered from prospective studies are lacking. METHODS: From 1997 to 1999, 177 patients were randomized to undergo LNF or CNF. Five years after surgery, all patients were requested to fill in questionnaires and to undergo esophageal manometry and 24-hour pH-metry. RESULTS: A total of 148 patients agreed to participate in the follow-up study: 79 patients after LNF and 69 after CNF. Of these, 97 patients (48 LNF, 49 CNF) consented to undergo esophageal manometry and 24-hour pH-metry. At 5 years follow-up, 20 patients had undergone reoperation: 12 after LNF (15%) and 8 after CNF (12%). There was no difference in subjective outcome, with overall satisfaction rates of 88% and 90%, respectively. Total esophageal acid exposure times (pH < 4) were 2.1% +/- 0.5% and 2.0% +/- 0.6%, respectively (P = 0.21). Antisecretory medication was taken daily in 14% and 16%, respectively (P = 0.29). There was no correlation between medication use and acid exposure and indices of symptom-reflux association (symptom index and symptom association probability). No significant differences between subjective and objective results at 3 to 6 months and results obtained at 5 years after surgery were found. CONCLUSIONS: The effects of LNF and CNF on general state of health and objective reflux control are sustained up to 5 years after surgery and the long-term results of LNF and CNF are comparable. A substantial minority of patients in both groups had a second antireflux operation or took antisecretory drugs, although the use of those medications did not appear to be related to abnormal esophageal acid exposure.