| Literature DB >> 35146022 |
Panagiotis Kiekkas1, Anastasios Tzenalis2, Vasiliki Gklava2, Nikolaos Stefanopoulos1, Gregorios Voyagis2, Diamanto Aretha2.
Abstract
Delayed admission of patients to the intensive care unit (ICU) is increasing worldwide and can be followed by adverse outcomes when critical care treatment is not provided timely. This systematic review and meta-analysis appraised and synthesized the published literature about the association between delayed ICU admission and mortality of adult patients. Articles published from inception up to August 2021 in English-language, peer-reviewed journals indexed in CINAHL, PubMed, Scopus, Cochrane Library, and Web of Science were searched by using key terms. Delayed ICU admission constituted the intervention, while mortality for any predefined time period was the outcome. Risk for bias was evaluated with the Newcastle-Ottawa Scale and additional criteria. Study findings were synthesized qualitatively, while the odds ratios (ORs) for mortality with 95% confidence intervals (CIs) were combined quantitatively. Thirty-four observational studies met inclusion criteria. Risk for bias was low in most studies. Unadjusted mortality was reported in 33 studies and was significantly higher in the delayed ICU admission group in 23 studies. Adjusted mortality was reported in 18 studies, and delayed ICU admission was independently associated with significantly higher mortality in 13 studies. Overall, pooled OR for mortality in case of delayed ICU admission was 1.61 (95% CI 1.44-1.81). Interstudy heterogeneity was high (I 2 = 66.96%). According to subgroup analysis, OR for mortality was remarkably higher in postoperative patients (OR, 2.44, 95% CI 1.49-4.01). These findings indicate that delayed ICU admission is significantly associated with mortality of critically ill adults and highlight the importance of providing timely critical care in non-ICU settings.Entities:
Mesh:
Year: 2022 PMID: 35146022 PMCID: PMC8822318 DOI: 10.1155/2022/4083494
Source DB: PubMed Journal: Biomed Res Int Impact factor: 3.411
Figure 1Study selection process: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Characteristics and assessment of risk for bias of included studies.
| Author (year) | Study design/country | Study population | Non-DA/DA group/incidence of DA | Significant differences in patient characteristics between non-DA and DA groups | NOS∗/RFB∗∗ |
|---|---|---|---|---|---|
| Agustin et al. [ | Retrospective, single-center/US | 287 ED pts with severe sepsis and septic shock | Pts with ED LOS < 6 hrs (150)/pts with ED LOS ≥ 6 hrs (137)/47.7% | DA pts had lower initial lactate level | 9/4 |
| Al-Qahtani et al. [ | Retrospective, single-center/Saudi Arabia | 940 ED pts | Pts with ED LOS < 6 hrs (227)/pts with ED LOS between 6 and 24 hrs (358) and >24 hrs (355)/75.9% | DA pts were older and had longer duration of mechanical ventilation | 9/3 |
| Arulkumaran et al. [ | Prospective, multicenter/UK | 195,428 medical/surgical ward, obstetric/intermediate care areas, ED, and OR pts | Pts immediately admitted (187,133)/pts remaining outside ICU for ≤4 hrs (6,198) and >4 hrs (2,097)/4.2% | Not reported | 8/1 |
| Bing-Hua [ | Retrospective, single-center/China | 2,279 postoperative pts | Pts immediately admitted (2,094)/pts boarding in PACU for ≤2, 2-4, 4-6, and >6 hrs (185)/8.1% | DA pts were older and more likely to have diabetes and chronic lung disease | 7/3 |
| Cardoso et al. [ | Prospective, single-center/Brazil | 401 ED and general ward pts | Pts immediately admitted (125)/pts admitted from wards after ≤72 hrs (276)/68.8% | DA pts had more comorbidities | 9/2 |
| Chalfin et al. [ | Retrospective, multicenter/US | 50,322 ED pts | Pts with ED LOS < 6 hrs (49,286)/pts with ED LOS ≥ 6 hrs (1,036)/2.1% | No differences were noted | 8/3 |
| Chiavone and Rasslan [ | Prospective, single-center/Brazil | 94 postoperative pts after emergency surgery | Pts boarding in surgical unit for ≤12 hrs after the end of surgery (23)/pts boarding in surgical unit for >12 hrs (71)/75.5% | No differences were noted | 6/4 |
| Choi et al. [ | Retrospective, multicenter/Republic of Korea | 439 ED pts > 65 years with infectious diseases | Pts with ED LOS ≤ 6 hrs (179)/pts with ED LOS > 6 hrs (260) and >24 hrs (86)/59.2% and 19.6%, respectively | Not reported | 8/4 |
| Churpek et al. [ | Retrospective, multicenter/US | 3,789 medical/surgical ward pts | Pts admitted within 6 hrs (2,055)/pts admitted after ≥6 hrs (1,734)/45.7% | DA pts were older | 8/2 |
| Flabouris et al. [ | Retrospective, single-center/Australia | 21,960 ED and general ward pts | Pts directly admitted from ED (21,481)/pts admitted from general wards (479)/2.2% | DA pts had higher clinical severity | 8/3 |
| García-Gigorro et al. [ | Prospective and retrospective, single-center/Spain | 269 ED pts | Pts with ED LOS ≤ 5 hrs (140)/pts with ED LOS > 5 hrs (129)/48.0% | Not reported | 6/4 |
| Gillies et al. [ | Retrospective, multicenter/UK | 13,591 postoperative pts (excluding cardiac surgery and neurosurgery) | Pts immediately admitted after surgery (1,116)/pts admitted from non-ICU settings after ≤7 days (12,475)/89.5% | DA pts were older and had higher operative severity and emergency surgical status | 9/1 |
| Hsieh et al. [ | Retrospective, single-center/Taiwan | 267 ED pts with acute respiratory failure | Pts with ED LOS ≤ 1 hr (196)/pts with ED LOS > 1 hr (71)/26.6% | Not reported | 7/5 |
| Hung et al. [ | Retrospective, single-center/Taiwan | 1,242 nontrauma ED pts with ventilatory support | Pts with ED LOS ≤ 4 hrs (337)/pts with ED LOS > 4 hrs (905)/72.9% | Not reported | 7/4 |
| Intas et al. [ | Prospective, single-center/Greece | 200 intubated ED pts | Pts with ED LOS < 6 hrs (60)/pts with ED LOS ≥ 6 hrs (140)/70.0% | More DA pts were female and medical, had higher age, were more likely to manifest fever, and received more medicines | 8/3 |
| Khan et al. [ | Retrospective, single-center/Pakistan | 325 ED pts | Pts with ED LOS ≤ 6 hrs (164)/pts with ED LOS > 6 hrs (161)/49.5% | DA pts had lower GCS scores, were less likely to have history of endocrine disease, and more likely to have history of CNS disease | 8/4 |
| Leong et al. [ | Retrospective, single-center/US | 4,282 ED, OR, and ward pts | Pts directly admitted from ED or OR (3,862)/pts admitted from wards after ≤24 hrs (420)/9.8% | No differences were noted | 8/3 |
| Liu et al. [ | Retrospective, multicenter/US | 36,298 ED and ward pts | Pts directly admitted from ED (29,929)/pts admitted from wards after ≤24 hrs (6,369)/17.5% | Not reported | 7/3 |
| Louriz et al. [ | Retrospective, single-center/Morocco | 256 ED pts | Pts immediately admitted from ED (110)/pts admitted from wards (146)/57.0% | DA pts were older and had more comorbidities | 8/4 |
| Molina et al. [ | Retrospective, single-center/Singapore | 698 ED and ward pts | Pts directly admitted from ED (490)/pts admitted from wards after ≤24 hrs (208)/29.8% | DA pts were older and less likely to undergo resuscitation or intubation in ED | 9/3 |
| O'Callaghan et al. [ | Retrospective, single-center/UK | 1,609 ED, OR, and ward pts | Pts immediately admitted from ED (1,460)/pts admitted from ED, OR, or wards after >3 hrs (149)/9.3% | DA pts were more likely to have respiratory failure | 8/3 |
| Parkhe et al. [ | Retrospective, single-center/Australia | 122 ED and ward pts | Pts directly admitted from ED (99)/pts admitted from wards after ≤24 hrs (23)/18.9% | DA pts were older, had higher clinical severity, and were more likely to have history of cardiac, respiratory, and gastrointestinal disease | 7/4 |
| Phua et al. [ | Retrospective, single-center/Singapore | 103 ED and general ward pts | Pts directly admitted from ED (54)/pts admitted from general wards after ≤72 hrs (49)/47.6% | DA pts were older and less likely to have unstable vital signs and had better mental status | 8/3 |
| Renaud et al. [ | Prospective, multicenter/US, France | 453 ED and medical ward pts | Pts directly admitted from ED (315)/pts admitted from medical wards after 2-3 days (138)/30.5% | DA pts were more likely to have cardiovascular disease or diabetes and less likely to have abnormal mental status, tachycardia, tachypnea, acidosis, and multilobar infiltrates | 9/1 |
| Santos et al. [ | Prospective, single-center/Brazil | 206 ED pts | Pts with ED LOS < 637 min (65)/pts with ED LOS ≥ 637 min (141)/67.5% | DA pts were older and more likely to need assistance | 7/4 |
| Serviá et al. [ | Prospective, single-center/Spain | 243 ED pts with severe trauma | Pts with ED LOS ≤ 120 min (122)/pts with ED LOS > 120 min (121)/49.8% | DA pts were older and less likely to manifest shock, be mechanically ventilated, and need blood transfusion and had higher injury severity | 8/3 |
| Simpson et al. [ | Retrospective, multicenter/UK | 12,268 ED, ward, and intermediate care areas pts | Pts directly admitted from ED (9,389)/pts admitted from wards or intermediate care areas (2,879)/23.5% | DA pts were older and more likely to have severe past medical history | 8/3 |
| Stohl et al. [ | Prospective, multinational | 3,175 pts of any hospital setting | Pts admitted within 4 hrs (2,754)/pts admitted after ≥4 hrs (421)/13.3% | Not reported | 8/2 |
| Tilluckdharry et al. [ | Prospective, single-center/US | 443 ED pts | Pts with ED LOS < 24 hrs (339)/pts with ED LOS ≥ 24 hrs (104)/23.5% | No differences were noted | 8/5 |
| Tsakiridou et al. [ | Prospective, single-center/Greece | 100 pts of any hospital setting with VAP | Pts admitted within 24 hrs (68)/pts admitted after ≥24 hrs (32)/32.0% | DA pts were more likely to be previously hospitalized and have chronic renal failure and received more antibiotics | 7/4 |
| Yergens et al. [ | Retrospective, multicenter/Canada | 1,770 ED pts with sepsis or severe sepsis | Pts with ED LOS ≤ 7 hrs (488)/pts with ED LOS > 7 hrs (1,282)/72.4% | DA pts were older and had higher triage level | 8/3 |
| Young et al. [ | Prospective, single-center/US | 91 ward pts with noncardiac diagnoses | Pts admitted within 4 hrs (35)/pts admitted after ≥4 hrs (56)/61.5% | No differences were noted | 8/3 |
| Zhang et al. [ | Retrospective, single-center/China | 1,997 ED pts with sepsis | Pts with ED LOS < 6 hrs (1,306)/pts with ED LOS ≥ 6 hrs (691)/34.6% | Not reported | 8/4 |
| Zhou et al. [ | Retrospective, single-center/China | 989 postoperative neurosurgical pts | Pts immediately admitted from OR (937)/pts boarding in PACU for ≤2 and >2 hrs (52)/5.3% | DA pts were less likely to be neurooncological | 6/4 |
ICU: intensive care unit; ED: emergency department, PACU: postanesthesia care unit; OR: operating room; LOS: length of stay; GCS: Glasgow Coma Scale; CNS: central nervous system; VAP: ventilator-associated pneumonia; DA: delayed ICU admission; NOS: Newcastle-Ottawa Scale; RFB: risk for bias according to additional criteria; pts: patients; hr: hour; min: minutes. ∗Score ranging from 0 to 9; the higher the score, the lower the risk for bias. ∗∗Score ranging from 0 to 7; the higher the score, the higher the risk for bias.
Findings of included studies.
| Author (year) | Unadjusted mortality (univariate associations) | Adjusted mortality (multivariate associations) |
|---|---|---|
| Agustin et al. [ | No significant difference in hospital mortality between pts with ED LOS ≥ 6 hrs and those with ED LOS < 6 hrs: 24.7% vs. 22.6%, OR 1.12, 95% CI 0.65-1.93, | ED LOS ≥ 6 hrs was not associated with higher hospital mortality: OR 1.23, 95% CI 0.67-2.25, |
| Al-Qahtani et al. [ | Pts with ED LOS between 6 and 24 hrs and >24 hrs had higher hospital mortality than those with ED LOS < 6 hrs: 29.1% and 37.2% vs. 22.5%, respectively, | ED LOS > 24 hrs was independently associated with higher hospital mortality: OR 2.09, 95% CI 1.22-3.60, |
| Arulkumaran et al. [ | Not reported | Remaining outside ICU for ≤4 hrs and >4 hrs were independently associated with higher hospital mortality: OR 1.08, 95% CI 1.01-1.17, and OR 1.17, 95% CI 1.04-1.32, |
| Bing-Hua [ | No significant difference in ICU mortality between pts immediately admitted to ICU and those boarding in PACU: 8.6% vs. 6.7%, | Boarding in PACU for >6 hrs was independently associated with higher ICU mortality: OR 5.32, 95% CI 1.25-22.60, |
| Cardoso et al. [ | Pts not immediately admitted to the ICU had higher ICU mortality than immediately admitted ones: 50.0% vs. 37.6%, OR 1.66, 95% CI 1.08-2.56, | Each hr of delayed ICU admission was independently associated with 1.0% increase in hospital mortality and 1.5% increase in ICU mortality: HR 1.01, 95% CI 1.00-1.02, |
| Chalfin et al. [ | Pts with ED LOS > 6 hrs had higher hospital and ICU mortality than those with ED LOS < 6 hrs: 17.4% vs. 12.9%, | ED LOS > 6 hrs was independently associated with higher hospital mortality: OR 1.41, 95% CI 1.12-1.78, |
| Chiavone and Rasslan [ | Pts with PACU LOS > 12 hrs had higher ICU mortality than those with PACU LOS ≤ 12 hrs: 54.9% vs. 26.1%, OR 3.45, 95% CI 1.22-9.78, | Not reported |
| Choi et al. [ | No significant difference in hospital mortality between pts with ED LOS > 6 hrs and those with ED LOS ≤ 6 hrs: 31.5% vs. 27.9%, OR 1.19, 95% CI 0.78-1.81, | ED LOS (as continuous variable) was independently associated with higher hospital mortality: OR 1.01, 95% CI 1.00-1.02, |
| Churpek et al. [ | Pts admitted to ICU after >6 hrs had higher hospital mortality than those admitted within 6 hrs: 33.2% vs. 24.5%, OR 1.53, 95% CI 1.33-1.77, | Each hr of delayed ICU admission was independently associated with 3.0% increase in hospital mortality, |
| Flabouris et al. [ | Pts initially admitted to general wards had higher hospital mortality than those directly admitted to ICU: 34.9% vs. 23.3%, OR 1.76, 95% CI 1.46-2.13, | Not reported |
| García-Gigorro et al. [ | Pts with ED LOS > 5 hrs had higher hospital and ICU mortality than those with ED LOS ≤ 5 hrs: 21.7% vs. 8.6%, | ED LOS > 5 hrs was independently associated with higher hospital mortality: OR 3.13, 95% CI 1.86-5.22 |
| Gillies et al. [ | Pts admitted to ICU after ≤7 days had higher hospital, perioperative (30-day), and ICU mortality than immediately admitted ones: 24.3% vs. 14.0%, | Admission to ICU after ≤7 days was independently associated with higher perioperative (30-day) mortality: OR 2.39, 95% CI 2.01-2.84, |
| Hsieh et al. [ | Pts with ED LOS > 1 hr had higher hospital mortality than those with ED LOS ≤ 1 hr: 84.5% vs. 71.4%, OR 2.18, 95% CI 1.07-4.45, | ED LOS > 1 hr was independently associated with higher hospital mortality: OR 2.19, 95% CI 1.04-4.64, |
| Hung et al. [ | No significant difference in 21-ventilator-day mortality between pts with ED LOS > 4 hrs and those with ED LOS ≤ 4 hrs: OR 1.17, 95% CI 0.98-1.39, | ED LOS > 4 hrs was independently associated with higher 21-ventilator-day mortality: OR 1.41, 95% CI 1.05-1.89, |
| Intas et al. [ | Pts with ED LOS ≥ 6 hrs had higher hospital and ICU mortality than those with ED LOS < 6 hrs: 62.9% vs. 46.7%, | ED LOS ≥ 6 hrs was independently associated with higher hospital mortality: OR 5.73, 95% CI 2.25-13.71, |
| Khan et al. [ | No significant difference in hospital mortality between pts with ED LOS > 6 hrs and those with ED LOS ≤ 6 hrs: 27.3% vs. 20.7%, OR 1.44, 95% CI 0.86-2.40, | Not reported |
| Leong et al. [ | Pts admitted to ICU after ≤24 hrs had higher 30-day and 90-day mortality than directly admitted ones: 15.0% vs. 9.9%, | Admission to ICU after ≤24 hrs was not associated with higher 30-day mortality: OR 0.84, 95% CI 0.60-1.17, |
| Liu et al. [ | Pts admitted to ICU after ≤24 hrs had higher hospital mortality than directly admitted ones: 11.6% vs. 8.5%, OR 1.41, 95% CI 1.30-1.54, | Not reported |
| Louriz et al. [ | No significant difference in hospital mortality between pts admitted from wards and immediately admitted ones: 43.8% vs. 33.3%, HR 1.11, 95% CI 0.74-1.68, | Delayed admission to ICU from wards was not associated with higher hospital mortality: OR 1.02, 95% CI 0.67-1.57, |
| Molina et al. [ | Pts admitted to ICU after ≤24 hrs had higher hospital and 60-day mortality than directly admitted ones: 32.2% vs. 27.0%, | Admission to ICU after ≤24 hrs was independently associated with higher hospital and 60-day mortality: OR 3.07, 95% CI 1.39-6.80, and OR 3.09, 95% CI 1.40-6.83, respectively |
| O'Callaghan et al. [ | No significant difference in hospital and ICU mortality between pts admitted to ICU after >3 hrs and directly admitted ones: 36.2% vs. 32.8%, | Admission to ICU after >3 hrs was not associated with higher ICU mortality: OR 1.27, 95% CI 0.81-2.01, |
| Parkhe et al. [ | Pts admitted to ICU after ≤24 hrs had higher hospital and ICU mortality than directly admitted ones: 34.8% vs. 14.1%, OR 3.5, 95% CI 1.5-7.8, | Not reported |
| Phua et al. [ | Pts admitted to ICU after ≤72 hrs had higher hospital mortality than directly admitted ones: 51.0% vs. 20.4%, | Admission to ICU after ≤72 hrs was independently associated with higher hospital mortality: OR 9.61, 95% CI 2.32-39.78, |
| Renaud et al. [ | No significant difference in 28-day mortality between pts admitted to ICU after 2-3 days and directly admitted ones: 19.6% vs. 13.6%, OR 1.54, 95% CI 0.91-2.61, | Admission to ICU after 2-3 days was independently associated with higher 28-day mortality: OR 2.48, 95% CI 1.21-5.08, |
| Santos et al. [ | No significant difference in hospital and ICU mortality between pts with ED LOS < 637 min and those with ED LOS ≥ 637 min: 30.8% vs. 36.9%, OR 1.31, 95% CI 0.70-2.46, | Not reported |
| Serviá et al. [ | Pts with ED LOS > 120 min had higher hospital mortality than those with ED LOS ≤ 120 min: 28.7% vs. 11.6%, OR 3.14, 95% CI 1.59-6.21, | ED LOS > 120 min was not associated with higher hospital mortality (OR not reported) |
| Simpson et al. [ | Pts not directly admitted to ICU had higher hospital and ICU mortality than directly admitted ones: 46.4% vs. 32.7%, OR 1.78, 95% CI 1.64-1.94, | Not reported |
| Stohl et al. [ | No significant difference in 28-day mortality between pts admitted to ICU after ≥4 hrs and those admitted within 4 hrs: 25.2% vs. 29.6%, OR 0.80, 95% CI 0.63-1.01, | Admission to ICU after ≥4 hrs was not associated with higher 28-day, hospital, ICU, and 3-month mortality: OR 1.10, 95% CI 0.85-1.43, |
| Tilluckdharry et al. [ | No significant difference in hospital mortality between pts with ED LOS ≥ 24 hrs and those with ED LOS < 24 hrs: 26.8% vs. 26.9%, OR 1.0, 95% CI 0.61-1.65, | Not reported |
| Tsakiridou et al. [ | No significant difference in hospital mortality between pts admitted to ICU after ≥24 hrs and those admitted within 24 hrs: 40.6% vs. 30.9%, OR 1.53, 95% CI 0.64-3.67, | Not reported |
| Yergens et al. [ | Pts with ED LOS > 7 hrs had higher hospital mortality than those with ED LOS ≤ 7 hrs: 74.6% vs. 66.4%, OR 1.48, 95% CI 1.18-1.86, | Not reported |
| Young et al. [ | Pts admitted after ≥4 hrs had higher hospital mortality than those admitted within 4 hrs: 41.1% vs. 11.4%, OR 5.40, 95% CI 1.68-17.39, | Not reported |
| Zhang et al. [ | Pts with ED LOS of 12-24 hrs and >24 hrs had higher hospital mortality than those with ED LOS < 6 hrs: 31.9% and 31.8% vs. 21.4%, | ED LOS of 12-24 hrs and >24 hrs was independently associated with higher hospital mortality: OR 1.82, 95% CI 1.28-2.58, |
| Zhou et al. [ | No significant difference in ICU mortality between pts immediately admitted to ICU and those boarding in PACU: 5.2% vs. 3.8%, | Not reported |
ICU: intensive care unit; ED: emergency department; PACU: postanesthesia care unit; LOS: length of stay; OR: odds ratio; HR: hazard ratio; CI: confidence interval; pts: patients; hr: hour; min: minutes.
Figure 2Funnel plot for the assessment of publication bias among studies that reported odds ratios (unadjusted or adjusted) for mortality according to delayed intensive care unit admission. Circles represent odds ratios coming from published studies.
Figure 3Forest plot depicting individual and pooled odds ratios for mortality with 95% confidence intervals according to delayed intensive care unit admission. OR: odds ratio; CI: confidence interval; hos: hospital; ICU: intensive care unit; 30 d: 30-day; 28 d: 28-day; 21 vd: 21-ventilator-day; adj: adjusted; un: unadjusted.
Subgroup and sensitivity analyses: pooled odds ratios for mortality according to delayed intensive care unit admission and 95% confidence intervals.
| Pooled odds ratio | 95% confidence interval | |
|---|---|---|
|
| ||
| Patients admitted from the emergency department ( | 1.64 | 1.38-1.94 |
| Patients admitted from the wards ( | 1.78 | 1.49-2.13 |
| Postoperative patients ( | 2.44 | 1.49-4.01 |
|
| ||
| Patients immediately/directly admitted to the ICU ( | 1.62 | 1.36-1.93 |
| Patients with shorter ICU admission delay than that of the delayed ICU admission group ( | 1.63 | 1.39-1.88 |
|
| ||
| Unadjusted ( | 1.59 | 1.42-1.79 |
| Adjusted ( | 1.71 | 1.38-2.12 |
| Hospital ( | 1.51 | 1.49-1.58 |
| ICU ( | 1.57 | 1.27-1.95 |
GRADE evidence profile.
| Outcome examined ( | Study design | Certainty assessment | Summary of findings | Certainty | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Risk for bias | Inconsistency | Indirectness | Imprecision | Publication bias | DA/non-DA pts ( | Relative effect (95% CI) | Absolute effects (95% CI) | ||||
| DA | Non-DA | ||||||||||
| Mortality | Observational cohort (⊕⊕⊕O) | Not serious | Serious | Not serious | Not serious | Not serious | 40,348/316,588 | OR, 1.61 (1.44, 1.81) | 271 per 1,000 (258-284) | 163 per 1,000 (154-172) | Low (⊕⊕OO) |
OR: odds ratio; CI: confidence interval; DA: delayed ICU admission; pts: patients.