Clinical outcomes of patients undergoing primary percutaneous coronary intervention for acute myocardial infarction requiring the intensive care unit

Clinical outcomes of patients undergoing primary percutaneous coronary intervention for acute... Background: Outcomes for patients with ST-segment elevation myocardial infarction continue to improve, largely due to timely provision of reperfusion by primary percutaneous coronary intervention (PPCI). However, despite prompt and successful PPCI, a small proportion of patients require ventilatory and hemodynamic support in an intensive care unit (ICU). The outcome of these patients remains poorly defined. Methods: A retrospective review of all consecutive admissions post-PPCI pathway to a single ICU between January 2009 and May 2014 was performed. Patients were analysed based on survival and indication for admission. Preadmission characteristics and ICU course were reviewed. Univariate and multivariable regression analysis was performed to determine predictors of outcome. Results: During the study period 2902 PPCI were performed and 101 patients were admitted to ICU following PPCI (incidence 3.5%). ICU mortality post-PPCI was 33.7%. Pre-ICU admission factors in a multivariable logistic regression analysis associated with increased mortality included requirement for an intra-aortic balloon pump and a high SOFA score. Conclusions: ICU admission post PPCI is associated with significant mortality. Mortality was related to high presenting SOFA score and need for IABP. These results provide important prognostic information and an acceptable method for risk-stratifying patients with acute myocardial infarction requiring intensive care. Keywords: Acute myocardial infarction, Primary percutaneous coronary intervention, Mechanical ventilation, Intensive care unit Background increase in PPCI volume and a reduction in hospital Acute myocardial infarction, in particular ST-segment mortality associated with STEMI [2, 3]. A major driver elevation myocardial infarction (STEMI) remains a time- to facilitate this has been the creation and implementa- sensitive medical emergency associated with significant tion of organised PPCI networks that are able to triage morbidity and mortality [1]. In recent years, the wide- and deliver patients directly to centres able to routinely spread recognition of primary percutaneous coronary provide this service both in- and out-of-hours [4, 5]. intervention (PPCI) as an evidence-based treatment Patients are subsequently generally cared for in a strategy that can improve outcomes has led to both an coronary-care unit (CCU), which has been shown to reduce mortality [6]. * Correspondence: ken.parhar@albertahealthservices.ca The National Infarct Angioplasty Project has demon- Department of Anesthesia and Intensive Care, Papworth Hospital, strated the benefits of PPCI over thrombolysis for treat- Cambridge, England 3 ment of STEMI patients [7] and has led to the creation Department of Critical Care Medicine, University of Calgary, ICU Administration - Ground Floor - McCaig Tower, Foothills Medical Center, of PPCI centres across England. By 2013, some regions 3134 Hospital Drive NW, Calgary, AB T2N 5A1, Canada demonstrated that more than 95% of patients treated for Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Parhar et al. Journal of Intensive Care (2018) 6:5 Page 2 of 10 STEMI received PPCI, compared with only 30% in the local database (Philips CVIS, Netherlands), routinely third quarter of 2008 [5]. collected for national audits, and patient case-notes Despite the pervasiveness of PPCI in the management where appropriate. ICU interventions, length of stay, of STEMI and the appropriate use of CCU care, there and complications were extracted from CIS. Survival remains a small proportion of patients that become data including the ICU and 28 day/hospital outcome critically ill and require advanced life support modalities was derived from both CIS, case notes and local data- post-PPCI, such as mechanical ventilation or vasoactive bases linked to national outcome data. therapy that may only be provided within the intensive Vital signs on admission (including heart rate, blood pres- care unit (ICU). Historically, patients with a complicated sure and mean arterial pressure) are reported as mean over myocardial infarction requiring mechanical ventilation the first 24 h of ICU admission. The admission PaO2 to have been associated with high rates of morbidity and FiO2 (PF) ratio, creatinine, platelets, bilirubin were the mortality [8–13]. worst value measured over the first 24 h. Pulmonary edema Patients that may require ICU post-PPCI remain was defined as hypoxemia with associated radiographic poorly defined. This retrospective single-centre cohort evidence of interstitial and/or alveolar edema. Cardiogenic review aims to describe the incidence of admission to shock was defined as a systolic blood pressure < 90 mmHg ICU, indication for ICU admission, and quantify the with clinical evidence of hypoperfusion (cyanosis, mottling, morbidity and mortality associated with ICU admission. oliguria, cold extremities) or the requirement for an In addition, factors associated with survival are assessed. inotrope. New onset renal dysfunction was defined as a 25% rise in serum creatinine or the requirement for renal Methods replacement therapy. The initiation of renal replacement Patient population therapy was based on refractory hyperkalemia, refractory We undertook a retrospective review of all consecutive acidosis, or volume overload despite medical management. patients admitted to a single tertiary cardiothoracic ICU Major hemorrhage was clinical evidence of bleeding with post-PPCI between January 2009 and May 2014. The the requirement for four or more units of red blood cells. unit is the sole provider of intensive care in a subspe- Infection was a positive culture result, or clinical syndrome cialty cardiothoracic hospital serving an English region consistent with infection such as pneumonia (fever, elevated with a catchment area of approximately three million. white cell count, purulent sputum, hypoxemia). Sequential All patients requiring PPCI in this region are transferred organ function failure assessment (SOFA) score was calcu- to this institution. lated as previously described [14, 15]. The search was performed via the electronic Clinical Information System (CIS), which maintains the elec- Groups tronic medical record of all patients admitted to ICU. Patient outcomes were analysed based on ICU survival. The initial search yielded 191 patients. Patients were Patient were stratified and analysed based on one of four excluded if not admitted directly post-PPCI. Ninety indications for ICU admission including out-of-hospital patients were excluded including: patients admitted cardiac arrest (OHCA), in-hospital cardiac arrest (IHCA), immediately before or after cardiac surgery or cardiac cardiogenic shock, or pulmonary edema. IHCA was procedures other than PPCI (n = 78), post respiratory defined as a cardiac arrest occurring following arrival to medicine procedures (n = 2), patients admitted due to hospital (most commonly during cardiac catheterization), lack of beds in CCU (n = 9), and patients admitted for but prior to admission to ICU. Cardiac arrests occurring end of life care (n = 1). A total of 101 patients post-PPCI while in ICU were listed as an ICU complication. were appropriate for detailed chart review and analysis (Fig. 1). Statistical analysis Clinical data The Shapiro-Wilks test for normality was performed on Demographic data (including age, gender, past medical all continuous variables. Continuous variables with normal history, and cardiovascular risk factors) were extracted distribution were reported as means with standard devi- from case-notes and the electronic CIS. Baseline physio- ation and analysed by unpaired student’s two-tailed t test logical characteristics (vital signs, Glasgow coma scale or one-way analysis of variance (ANOVA) where appro- (GCS), laboratory values) were extracted from the priate. Non-normally-distributed data were reported as electronic CIS. Details related to PPCI admission, echo- median with interquartile range and analysed with the cardiograms, and cardiac catheterization (downtime, Mann-Whitney U test or the Kruskal-Wallis test where location of infarction, procedures performed, anatomy of appropriate. Categorical variables were analysed with the coronary disease, complications, door-to-balloon time, chi-squared test or Fisher’s exact test where appropriate. pre-PCI interventions) were extracted from a dedicated A p value of < 0.05 was considered statistically significant. Parhar et al. Journal of Intensive Care (2018) 6:5 Page 3 of 10 Fig. 1 Flowchart outlining patient selection Variables that were statistically significant in the uni- Of the 101 patients who were admitted to ICU, the variate analysis (with a p value < 0.10) were considered majority were male (69%), with a mean age of 65 years for inclusion in the multivariable logistic regression (Table 1). Out of hospital cardiac arrest (OHCA) was the model. ICU mortality was defined as the dependant most common indication for admission to ICU (36.6%). A variable. Backward stepwise variable elimination was significant proportion of patients were admitted for in- performed (with a variable exit threshold set at p > 0.05). hospital cardiac arrest (IHCA; 31.7%) and cardiogenic The performance of the final model was assessed using shock (22.8%). The least common indication for admission the area under the receiver-operating characteristic to ICU post-PPCI was pulmonary edema (8.9%). Overall (AUROC) curve. ICU mortality was 33.7% for the entire cohort. Statistical analysis was performed using Stata Version Univariate factors that demonstrated a statistically signifi- 13.1 (StataCorp, USA). cant difference between survivors and non-survivors included age, low blood pressure on admission (both Ethics systolic and mean arterial pressure), low PF ratio, low GCS, Ethical approval was obtained from the Papworth Hospital high creatinine, and high SOFA scores. In the subgroup of NHS Foundation Trust research and development board patients suffering from an OHCA, downtime before return for the completion of this study. of spontaneous circulation (ROSC) was statistically differ- ent between survivors and non-survivors. Survivors of ICU Results post PPCI were associated with a shorter downtime in One-hundred one patients met the inclusion criteria for comparison to non-survivors (Fig. 2). Patients who suffered this retrospective observational study (Fig. 1). During awitnessed IHCA didnot demonstrate a difference in time this time, a total of 2902 PPCI were performed, resulting to ROSC between survivors and non-survivors. When in a post-PPCI incidence of admission to ICU post PPCI patients were stratified based on their indication for admis- of 3.5%. sion (OHCA, IHCA, shock, or pulmonary edema) to ICU Parhar et al. Journal of Intensive Care (2018) 6:5 Page 4 of 10 Table 1 Patient demographic factors for patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All patients Outcome Indication for ICU Survivor Non-survivor Sign OHCA IHCA Card shock Pulm edema Sign Total no of patients (%) 101 (100) 67 (66.3) 34 (33.7) 37 (36.6) 32 (31.7) 23 (22.8) 9 (8.9) Gender Male, no (%) 70 (69.3) 48 (47.5) 22 (21.8) 0.500 29 (28.7) 20 (19.8) 15 (14.9) 6 (5.9) 0.505 Age, years 65.3 (12.8) 63.8 (11.5) 68.3 (14.8) 0.047 60.2 (12.8) 66.8 (12.6) 71.2 (10.7) 66.0 (11.8) 0.009 Cardiovascular risk factors Smoking, no (%) 28 (27.7) 19 (18.8) 9 (8.91) 1.000 11 (10.9) 11 (10.9) 3 (3.0) 3 (3.0) 0.335 Diabetes mellitus, no (%) 21 (20.8) 10 (9.9) 11(10.9) 0.067 4 (4.0) 7 (6.9) 8 (7.9) 2 (2.0) 0.171 Dyslipidaemia, no (%) 30 (29.7) 22 (21.8) 8 (7.9) 0.367 8 (7.9) 10 (9.9) 9 (8.9) 3 (3.0) 0.526 Hypertension, no (%) 58 (57.4) 40 (39.6) 18 (17.8) 0.531 18 (17.8) 17 (16.8) 16 (15.8) 7 (6.9) 0.229 Past medical history Previous MI, no (%) 20 (19.8) 15 (14.9) 5 (5.0) 0.436 3 (3.0) 4 (4.0) 8 (7.9) 5 (5.0) 0.002 Previous CAD, no (%) 29 (28.7) 21 (20.8) 8 (7.9) 0.490 4 (4.0) 9 (8.9) 10 (9.9) 6 (5.9) 0.002 Previous CHF, no (%) 3 (3.0) 2 (2.0) 1 (1.0) 1.000 0 (0.0) 1 (1.0) 1 (1.0) 1 (1.0) 0.340 Renal failure, no (%) 12 (11.9) 8 (7.9) 4 (4.0) 1.000 3 (3.0) 2 (2.0) 5 (5.0) 2 (2.0) 0.210 COPD no, no (%) 11 (10.9) 9 (8.9) 2 (2.0) 0.326 3 (3.0) 6 (5.9) 0 (0.0) 2 (2.0) 0.096 Baseline characteristics on admission HR (bpm) 79.7 (15.6) 78.5 (16.0) 82.0 (14.5) 0.297 70.6 (15) 80.4 (12.3) 87.8 (13.4) 93.8 (11.7) < 0.001 Systolic BP (mmHg) 106.8 (19.5) 111.8 (17.9) 96.3 (18.7) < 0.001 106.9 (16.4) 103.16 (20.7) 108.9 (21.2) 114.0 (22.2) 0.462 MAP (mmHg) 73.0 (13.0) 77.7 (10.3) 63.7 (12.9) < 0.001 72.5 (12.4) 73.7 (15.3) 71.4 (9.5) 77.0 (15.0) 0.720 PaO2/FiO2 ratio, med (IQR) 143 (98–233) 154 (98–271) 105 (83–173) 0.036 157.9 (105–241) 165 (83–286) 105 (83–143) 128 (75–278) 0.138 GCS, med (IQR) 3 (3–15) 11 (3–15) 3 (3–3) < 0.001 3 (3–4) 3 (3–14.5) 14 (3–15) 3 (3–15) 0.071 Serum creatinine (μmol/L), med (IQR) 116 (87–157) 102 (84–129) 156 (115–203) < 0.001 101 (71–126) 116 (95–155) 140 (112–191) 135 (117–144) 0.012 SOFA score 8.4 (3.3) 7.4 (2.9) 10.4 (3.1) < 0.001 8.6 (2.6) 8.5 (3.5) 8.3 (3.4) 8.0 (5.2) 0.953 Indication for ICU admission OHCA, no (%) 37 (36.6) 26 (25.7) 11 (10.9) 0.663 Downtime before ROSC (min), (IQR) 20 (15–30) 15 (10–20) 35 (30–40) < 0.001 IHCA, no (%) 32 (31.7) 19 (18.8) 13 (12.7) 0.368 Downtime before ROSC (min), (IQR) 10 (5–20) 9 (5–14) 15 (5–42) 0.214 Cardiogenic shock, no (%) 23 (22.8) 14 (13.9) 9 (8.9) 0.617 Acute pulmonary oedema, no (%) 9 (8.9) 8 (7.9) 1 (1.0) 0.266 post PPCI, there was no difference in mortality amongst with reduced survival included severe LV dysfunction, right the four groups. ventricle (RV) involvement, and the need for intra-aortic STEMI was the most common type of presenting balloon pump (IABP) insertion in the cath lab. The indica- acute coronary syndrome (91%) (Table 2). Other patients tions for IABP insertion in the cath lab included cardio- who underwent PPCI had either indeterminate ACS genic shock, bridge for high risk PCI, and ongoing chest (due to a left bundle branch block) or a high suspicion pain. IABP were all inserted prior to admission to ICU. The of an evolving transmural infarct. The majority were in cardiologic factors did not influence the indication for the anterior territory (61%) and uncommonly involved admission to ICU (Additional file 1:Table S1). the right ventricle (5.0%). Left ventricular (LV) systolic The median duration of stay in the ICU was 3 days function was depressed in the majority of patients with (Table 3). Most patients required invasive mechanical over 50% of patients having either moderate or severe ventilation (IMV) (86.1%) with median duration of IMV LV dysfunction as determined by echocardiography dur- being 2 days. The majority of the mortality occurred ing admission. Only one patient received thrombolytics within the ICU (34 of 37 patients). Significant complica- prior to PPCI. Angiogram was successfully performed in tions were common with patients suffering major bleeding the majority of patients (98.0%) with the exception of (9.9%), infections (31.7%), acute kidney injury (33.7%), or two patients in whom it was attempted but aborted due in ICU cardiac arrest (6.9%). Factors that statistically asso- to cardiac arrest. There was a high rate of PCI per- ciated with reduced survival included the lack of use of formed (90.1%). Factors that were statistically associated non-invasive ventilation (NIV), inotropes and vasopressor Parhar et al. Journal of Intensive Care (2018) 6:5 Page 5 of 10 Fig. 2 Box and whisker plots of the effect of downtime on return of spontaneous circulation in OHCA patients Table 2 Cardiac characteristics of patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All Patients Outcome Survivor Non-survivor Sign Total number of patients (%) 101 (100) 67 (66.3) 34 (33.7) STEMI, no (%) 91 (90.1) 58 (57.4) 33 (32.7) 0.158 MI territory Anterior, no (%) 61 (61.0) 42 (42.0) 19 (19.0) 0.667 Inferior, no (%) 38 (38.0) 26 (26.0) 12 (12.0) 1.000 Lateral, no (%) 32 (32.0) 22 (22.0) 10 (10.0) 1.000 RV involvement, no (%) 5 (5.0) 1 (1.0) 4 (4.0) 0.040 Peak troponin, ng/L med (IQR) 38.9 (13.7–40.0) 26.8 (10.9–40.0) 40.0 (19.1–626.0) 0.146 LV systolic function Normal, no (%) 10 (11.6) 8 (9.3) 2 (2.3) 0.488 Mild dysfunction, no (%) 26 (30.2) 21 (24.4) 5 (5.8) 0.093 Moderate dysfunction, no (%) 22 (25.6) 17 (19.8) 5 (5.8) 0.309 Severe dysfunction, no (%) 28 (32.6) 14 (16.3) 14 (16.3) 0.037 Thrombolysis pre-PPCI, no (%) 1 (1.0) 1 (1.0) 0 (0.0) 1.000 Angiogram, (successful completion) no (%) 99 (98.0) 67 (66.3) 32 (31.7) 0.111 PCI performed (successful completion), no (%) 91 (90.1) 62 (61.4) 29 (28.7) 0.298 IABP in cath lab, no (%) 50 (49.5) 28 (27.7) 22 (21.8) 0.036 Number of diseased vessels, med (IQR) 2 (1–3) 2 (1–3) 2 (2–3) 0.514 Left main stem disease, no (%) 14 (14.1) 8 (8.1) 6 (6.1) 0.371 TIMI flow, med (IQR) 3 (2–3) 3 (2–3) 3 (2–3) 0.862 Symptom onset to device time (min, med (IQR) 210 (155–332) 219 (159–328) 200 (150–350) 0.665 Parhar et al. Journal of Intensive Care (2018) 6:5 Page 6 of 10 Table 3 Intensive care characteristics and complications of patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All Outcome Indication for ICU patients Survivor Non-survivor Sign OHCA IHCA Card shock Pulm edema Sign Total number of patients (%) 101 (100) 67 (66.3) 34 (33.7) 37 (36.6) 32 (31.7) 23 (22.8) 9 (8.9) ICU interventions Invasive mechanical ventilation, no (%) 87 (86.1) 56 (55.5) 31 (30.7) 0.373 37 (36.6) 31 (30.7) 12 (11.9) 7 (6.9) < 0.001 Duration of IMV, median days (IQR) 2 (1–3) 2 (1–2) 2 (1–6) 0.314 2 (2–4) 1 (1–2) 2 (1–5) 1 (1–1) 0.011 Non-invasive ventilation, no (%) 25 (24.8) 21 (20.8) 4 (4.0) 0.049 7 (6.9) 5 (5.0) 8 (7.9) 5 (5.0) 0.047 Duration of NIV, median days (IQR) 1 (1–2) 1 (1–2) 2.5 (1.5–3) 0.075 1 (1–1) 2 (1–2) 2 (1.5–3) 1 (1–1) 0.032 Inotropes, median number (IQR) 1 (0–1) 0 (0–1) 1 (0–2) 0.005 1 (0–1) 1 (0–2) 0 (0–1) 0 (0–1) 0.617 Vasopressors, median number (IQR) 0 (0–1) 0 (0–1) 1 (0–1) 0.001 0 (0–1) 0 (0–1) 0 (0–1) 0 (0–1) 0.971 ECMO, no (%) 7 (6.9) 1 (1.0) 6 (5.9) 0.006 0 (0.0) 7 (6.9) 0 (0.0) 0 (0.0) 0.001 Therapeutic hypothermia, no (%) 48 (47.5) 33 (32.7) 15 (14.9) 0.677 32 (31.7) 14 (13.9) 0 (0.0) 2 (2.0) < 0.001 IABP, no (%) 59 (58.4) 35 (34.7) 24 (23.8) 0.090 15 (14.9) 23 (22.8) 18 (17.8) 3 (3.0) 0.004 Renal repl therapy, no (%) 27 (26.7) 10 (9.9) 17 (16.8) < 0.001 6 (5.9) 11 (10.9) 8 (7.9) 2 (2.0) 0.273 In-hospital complications Major bleeding, no (%) 10 (9.9) 6 (5.9) 4 (4.0) 0.082 0 (0.0) 7 (6.9) 2 (2.0) 1 (1.0) 0.026 Infections, no (%) 32 (31.7) 21 (20.8) 11 (10.9) 1.000 13 (12.9) 9 (8.9) 7 (6.9) 3 (3.0) 0.936 Renal dysfunction (new onset), no (%) 34 (33.7) 18 (17.8) 16 (15.8) 0.048 12 (11.9) 11 (10.9) 9 (8.9) 2 (2.0) 0.833 In ICU Cardiopulmonary arrest, no (%) 7 (6.9) 0 (0.0) 7 (6.9) < 0.001 3 (3.0) 4 (4.0) 0 (0.0) 0 (0.0) 0.261 Outcomes Duration of ICU stay, median days (IQR) 3 (1–5) 3 (1–4) 2 (0.5–7) 0.389 3 (2–7) 2 (1–5) 3 (0.5–5) 1 (0.5–2) 0.095 ICU mortality, no (%) 34 (33.7) 11 (10.9) 13 (12.9) 9 (8.9) 1 (1.0) 0.346 Hospital / 28-day mortality, no (%) 37 (36.6) 12 (11.9) 14 (13.9) 10 (9.9) 1 (1.0) 0.265 Cause of death (of 37 patients) Treatment withdrawn, no (%) 25 (67.6) 7 (18.9) 9 (24.3) 8 (21.6) 1 (2.7) 0.632 Cardiac Arrest, no (%) 7 (18.9) 3 (8.1) 2 (5.4) 2 (5.4) 0 (0.0) 0.867 Other 5 (13.5) 2 (5.4) 3 (8.1) 0 (0.0) 0 (0.0) 0.463 use, transfusion of blood products including red blood cells in multivariable regression analysis. Factors that were in- (RBCs) and nonRBCs, as well as need for extracorporeal dependently associated with ICU mortality included high membrane oxygenation (ECMO) or renal replacement SOFA score and pre-ICU insertion of an IABP (Table 4). therapy (RRT). ECMO was used exclusively in patients who Notable factors that were not independently associate with sufferedIHCAatany pointduringthe ICUadmission. mortality included age, presence of RV dysfunction, and Therapeutic hypothermia was used in patients who suffered presence of severe LV dysfunction. The odds ratio (OR) either OHCA or IHCA in patients with an initial rhythm of for increased mortality for each point increase in SOFA ventricular tachycardia or ventricular fibrillation, but was was 1.43 (95% CI 1.2–1.7). The OR for increased mortality not associated with a statistically significant increase in when an IABP was inserted pre-ICU admission (during survival. There were higher than expected rates of bleeding cardiac catheterization) was 3.38 (95% CI 1.27–9.03). The and transfusions (RBC) in the IHCA group. sensitivity and specificity of this model was 50 and 91% Twenty-eight-day mortality was similar to ICU mortality respectively with a positive predictive value (PPV) of 73.9% (Table 3, 36.6 vs 33.7%). The cause of death in most patients was withdrawal of care (67.6%). Post ICU admis- Table 4 Multivariable logistic regression analysis of factors sion cardiac arrest occurred in seven patients (18.9%), none associated with ICU mortality of whom survived. Odds ratio Standard error zP value 95% CI Pre-ICU admission factors that demonstrated a statisti- SOFA 1.43 0.127 4.01 0.000 1.200–1.700 cally significant difference between survivors and non- IABP 3.38 1.695 2.43 0.015 1.266–9.030 survivors in univariate analysis were selected for inclusion Parhar et al. Journal of Intensive Care (2018) 6:5 Page 7 of 10 and a negative predictive value (NPV) of 78.2%. This model shock following complicated myocardial infarction, our correctly classified 77.2% of patients in this series and had study reviewed consecutive patients admitted to ICU an AUROC curve of 0.7842 (Fig. 3). When using a model exclusively via the PPCI pathway [8–13, 16, 17]. This with only SOFA and without IABP, the AUROC was included both patients who required mechanical ventila- slightly lower (0.75 CI 0.65–0.85) in comparison to tion and those who did not. the model with SOFA and IABP (0.78 CI 0.68–0.89). A higher SOFA score was associated with increased mortality (Table 4). This suggests that degree of organ Discussion dysfunction in patients with complicated myocardial In this retrospective observational study, we present a infarction, as with many other critical illnesses, is a series of consecutive patients post-PPCI pathway that major determinant of survival. Surprisingly, neither the are critically ill and require admission to the ICU for requirement for mechanical ventilation nor the indica- advanced therapies that may only be provided in ICU tion for admission were independently associated with such as invasive mechanical ventilation or vasoactive mortality. To date, no study has described this relation- support. There is a significant mortality amongst these ship exclusively in the post-PPCI patient population. A patients (33.6%), which is significantly higher than the previous study looking at traditional risks scores used in general PPCI population. Indication for admission the myocardial infarction population such as the Global (cardiac arrest, pulmonary edema, cardiogenic shock) Registry of Acute Coronary Events (GRACE) risk score does not statistically influence mortality and all groups or the Thrombolysis in Myocardial Infarction (TIMI) were similar despite their indication. Those patients risk score in comparison with SOFA demonstrated that presenting with higher SOFA scores (reflecting a higher SOFA provided reasonable discrimination of prognosis degree of multiple-organ dysfunction), or requiring an [18]. This study was limited, as it did not focus on the IABP during cardiac catheterization were independently post-PPCI population or those patients specifically who associated with higher mortality. were admitted to ICU, which are most likely to be critic- Despite an era of appropriate anti-ischemic therapy ally ill and potentially benefit from prognostication. Our post-STEMI and provision of organised and timely study is novel as we demonstrate that the SOFA score reperfusion via PPCI, there remain a proportion of does predict mortality in this high-risk group of patients patients who become critically ill and require admission admitted to the ICU who require mechanical ventilation to ICU for invasive monitoring, mechanical ventilation and vasopressors. Previous studies looking specifically at or vasoactive therapy. Patient mortality in this group patients admitted to ICU with cardiogenic shock demon- remains high despite improving outcome for all patients strated that there was an association between scores such with STEMI presenting for PPCI [3]. as Acute Physiology and Chronic Health II/III (APACHE In contrast to previous studies of patients requiring II/III), Simplified Acute Physiology Score II (SAPSII), mechanical ventilation or suffering from cardiogenic SOFA and survival outcome [16, 17]. The specific organ Fig. 3 Area under the receiver operating curver (AUROC) of multivariable logistic regression model using IABP and SOFA Parhar et al. Journal of Intensive Care (2018) 6:5 Page 8 of 10 systems within the SOFA score that were responsible for (E-CPR). The IHCA group had a high rate of major the higher scores included increased renal dysfunction, bleeding most likely associated with the use of E-CPR, lower admission GCS, as well as worse hypoxemia (lower as this association is a well described in other ECMO PaO2/FiO2 ratio (Table 1). The benefit of using SOFA populations [26]. Survival in this group was low which is scores and the presence or absence of IABP to prognosti- consistent with previously published reviews on the use cate patients is that it can be easily calculated upon admis- of E-CPR in this age demographic [27]. sion to ICU with information routinely available. This is This study had several limitations. It was performed at the drawback of scores such as APACHE II/III and SAPSII a single tertiary PPCI referral centre and is retrospective as they are more complex and time consuming to calcu- in nature and thus data collection was based on review late when compared to SOFA [19]. SOFA was used as a of the CIS and paper charts. The multivariable logistic prognostic score due to its simplicity and ability to be regression model was not externally validated in an calculated with very routine and objective patient data. alternate population or in patients not admitted to ICU. Retrospective data collection made it difficult to use alter- Furthermore, there may be selection bias for patients nate scores such as APACHE II due to the high number requiring mechanical circulatory support with IABP due of variables required in these scores including patient to differences in individual clinical practice patterns. historical factors and the risk of missing data [19]. For This study provides a rationale for a future prospective example, any missing data precluded patients from being observational study and validation of the multivariable included in APACHE II score calculation as per the model to determine if this may help triage and prognos- original description of APACHE II [20]. In addition, it has ticate patients who are not likely to survive post compli- been demonstrated that there are significant differences in cated acute myocardial infarction. Potential uses for this the ability of APACHE II to be calculated accurately when type of model include being able to provide prognostic comparing prospective and retrospective collection of data information for care providers and patient family [21]. This further highlights the strength of the SOFA members. It may also help identify patients in whom score as it is quick and easy to calculate using commonly aggressive care may be deemed unlikely to succeed. available objective clinical data. Alternatively, if these patients are identified correctly a We demonstrated that use of IABP was independently priori, it may allow a targeted intervention to improve associated with mortality which is in keeping with previ- outcomes in this cohort of patients who continue to ously reported observational data [22, 23]. The cohort of have an extremely poor outcome. the study patients who required mechanical circulatory support with IABP and ICU admission was representa- Conclusions tive of the higher risk patient population and therefore Despite only requiring admission 3.5% of the time to IABP support may have been given to the sicker patients ICU (101 of 2902 patients), those patients suffering an which would induce bias towards poor outcomes in that MI that do require ICU post PPCI are very critically ill group. A meta-analysis of cohort studies in the context and have a mortality of 33.7%. The most effective way to of STEMI leading to cardiogenic shock supported the prognosticate survival in this cohort of patients is by use of IABP adjunctive to fibrinolysis [24]. It remains using the SOFA score, in addition to the requirement unknown whether early IABP placement can improve for an intra-aortic balloon pump. clinically important outcomes in patients with STEMI requiring ICU admission. In the subgroup of patients with an OHCA, a longer Additional file down time before ROSC was associated with higher Additional file 1: Table S1. Cardiac characteristics of patients admitted mortality; however, in the multivariable analysis, this was to ICU post PPCI by indication. Results are expressed as mean (SD) unless not an independent predictor for increased mortality. otherwise denoted. (DOCX 17 kb) The association between prompt ROSC and outcome has been well described previously [25]. Similarly age Abbreviations was a univariate factor associated with increased mortal- ANOVA: Analysis of variance; APACHE: Acute physiology and chronic health; ity however was not an independent predictor in the AUROC: Area under the receiver operating curve; CAD: Coronary artery disease; multivariable analysis. It may be that increased age and CCU: Coronary care unit; CIS: Clinical information system; ECMO: Extracorporeal membrane oxygenation; E-CPR: Ecmo during cardio-pulmonary resuscitation; longer downtimes before ROSC are all reflective of GCS: Glasgow coma scale; IABP: Intra-aortic balloon pump; ICU: Intensive care increased likelihood of organ dysfunction and a higher unit; IHCA: In-hospital cardiac arrest; IMV: Invasive mechanical ventilation; SOFA score, thus not independently associated with LV: Left ventricle; NIV: Non-invasive mechanical ventilation; NPV: Negative predictive value; OHCA: Out of hospital cardiac arrest; OR: Odds ratio; mortality. PF: PaO2:FiO2; PPCI: Primary percutaneous coronary intervention; PPV: Positive In the IHCA group, there were five patients who were predictive value; RBC: Red blood cells; ROSC: Return of spontaneous circulation; supported with ECMO under cardiac arrest conditions RRT: Renal replacement therapy; RV: Right ventricle; SAPSII: Simplified acute Parhar et al. Journal of Intensive Care (2018) 6:5 Page 9 of 10 physiology score II; SOFA: Sequential organ failure assessment; STEMI: ST-segment 6. Rotstein Z, Mandelzweig L, Lavi B, Eldar M, Gottlieb S, Hod H. Does the elevation myocardial infarction coronary care unit improve prognosis of patients with acute myocardial infarction? A thrombolytic era study. Eur Heart J. 1999;20:813–8. 7. McLenachan JM, Gray HH, de Belder MA, Ludman PF, Cunningham D, Acknowledgements Birkhead J. Developing primary PCI as a national reperfusion strategy for Thank Dr. Dan Niven with advice on statistical analysis with this manuscript. patients with ST-elevation myocardial infarction: the UK experience. EuroIntervention. 2012;8(Suppl P):P99–107. Funding 8. Ariza Sole A, Salazar-Mendiguchia J, Lorente-Tordera V, Sanchez-Salado JC, This research did not receive any specific grant from funding agencies in the Gonzalez-Costello J, Moliner-Borja P, Gomez-Hospital JA, Manito-Lorite N, public, commercial, or not-for-profit sectors. Cequier-Fillat A. Invasive mechanical ventilation in acute coronary syndromes in the era of percutaneous coronary intervention. Eur Heart J Availability of data and materials Acute Cardiovasc Care. 2013;2:109–17. The datasets generated and/or analysed during the current study are not 9. Lopez Messa JB, Andres De Llano JM, Berrocal De La Fuente CA, Pascual publicly available due to privacy and ethics compliance but are available Palacin R, Analisis Retraso Infarto Agudo M. Characteristics of acute from the corresponding author on reasonable request. myocardial infarction patients treated with mechanical ventilation. Data from the ARIAM registry. Rev Esp Cardiol. 2001;54:851–9. Author’s contributions 10. Kouraki K, Schneider S, Uebis R, Tebbe U, Klein HH, Janssens U, Zahn R, KP, KJ, VM, EB, and VZ contributed to data collection. KP, VZ, NW, and AV were Senges J, Zeymer U. Characteristics and clinical outcome of 458 patients involved in the study design, statistical methodology, interpretation of results, and with acute myocardial infarction requiring mechanical ventilation. Results of writing of the manuscript. All authors read and approved the final manuscript. the BEAT registry of the ALKK-study group. Clin Res Cardiol. 2011;100:235–9. 11. Zahger D, Maimon N, Novack V, Wolak A, Friger M, Gilutz H, Ilia R, Almog Y. Ethics approval and consent to participate Clinical characteristics and prognostic factors in patients with complicated Ethical approval was obtained from the Papworth Hospital NHS Foundation acute coronary syndromes requiring prolonged mechanical ventilation. Am Trust research and development board for the completion of this study. J Cardiol. 2005;96:1644–8. 12. Lesage A, Ramakers M, Daubin C, Verrier V, Beynier D, Charbonneau P, du Cheyron D. Complicated acute myocardial infarction requiring mechanical Consent for publication ventilation in the intensive care unit: prognostic factors of clinical outcome Not applicable in a series of 157 patients. Crit Care Med. 2004;32:100–5. 13. Eran O, Novack V, Gilutz H, Zahger D. Comparison of thrombolysis in Competing interests myocardial infarction, global registry of acute coronary events, and acute The authors declare that they have no competing interests. physiology and chronic health evaluation II risk scores in patients with acute myocardial infarction who require mechanical ventilation for more than 24 hours. Am J Cardiol. 2011;107:343–6. Publisher’sNote 14. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Springer Nature remains neutral with regard to jurisdictional claims in Reinhart CK, Suter PM, Thijs LG. The SOFA (sepsis-related organ failure published maps and institutional affiliations. assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Author details Intensive Care Medicine. Intensive Care Med. 1996;22:707–10. Department of Anesthesia and Intensive Care, Papworth Hospital, 15. 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O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, pitfalls in the use of APACHE II and suggestions for improvement. Ettinger SM, Fang JC, Fesmire FM, Franklin BA, et al. 2013 ACCF/AHA Anaesthesia. 2001;56:47–50. guideline for the management of ST-elevation myocardial infarction: 22. Zeymer U, Bauer T, Hamm C, Zahn R, Weidinger F, Seabra-Gomes R, executive summary: a report of the American College of Cardiology Hochadel M, Marco J, Gitt A. Use and impact of intra-aortic balloon pump Foundation/American Heart Association task force on practice guidelines. on mortality in patients with acute myocardial infarction complicated by Circulation. 2013;127:529–55. cardiogenic shock: results of the euro heart survey on PCI. EuroIntervention. 5. de Belder MA, Ludman PF, McLenachan JM, Weston CF, Cunningham D, 2011;7:437–41. Lazaridis EN, Gray HH. The national infarct angioplasty project: UK 23. Zeymer U, Hochadel M, Hauptmann KE, Wiegand K, Schuhmacher B, experience and subsequent developments. EuroIntervention. 2014; Brachmann J, Gitt A, Zahn R. Intra-aortic balloon pump in patients with 10(Suppl T):T96–T104. Parhar et al. Journal of Intensive Care (2018) 6:5 Page 10 of 10 acute myocardial infarction complicated by cardiogenic shock: results of the ALKK-PCI registry. Clin Res Cardiol. 2013;102:223–7. 24. Sjauw KD, Engstrom AE, Vis MM, van der Schaaf RJ, Baan J Jr, Koch KT, de Winter RJ, Piek JJ, Tijssen JG, Henriques JP. A systematic review and meta- analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines? Eur Heart J. 2009;30:459–68. 25. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out- of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010;3:63–81. 26. 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Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries � Our selector tool helps you to find the most relevant journal � We provide round the clock customer support � Convenient online submission � Thorough peer review � Inclusion in PubMed and all major indexing services � Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Intensive Care Springer Journals

Clinical outcomes of patients undergoing primary percutaneous coronary intervention for acute myocardial infarction requiring the intensive care unit

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Medicine & Public Health; Intensive / Critical Care Medicine
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Abstract

Background: Outcomes for patients with ST-segment elevation myocardial infarction continue to improve, largely due to timely provision of reperfusion by primary percutaneous coronary intervention (PPCI). However, despite prompt and successful PPCI, a small proportion of patients require ventilatory and hemodynamic support in an intensive care unit (ICU). The outcome of these patients remains poorly defined. Methods: A retrospective review of all consecutive admissions post-PPCI pathway to a single ICU between January 2009 and May 2014 was performed. Patients were analysed based on survival and indication for admission. Preadmission characteristics and ICU course were reviewed. Univariate and multivariable regression analysis was performed to determine predictors of outcome. Results: During the study period 2902 PPCI were performed and 101 patients were admitted to ICU following PPCI (incidence 3.5%). ICU mortality post-PPCI was 33.7%. Pre-ICU admission factors in a multivariable logistic regression analysis associated with increased mortality included requirement for an intra-aortic balloon pump and a high SOFA score. Conclusions: ICU admission post PPCI is associated with significant mortality. Mortality was related to high presenting SOFA score and need for IABP. These results provide important prognostic information and an acceptable method for risk-stratifying patients with acute myocardial infarction requiring intensive care. Keywords: Acute myocardial infarction, Primary percutaneous coronary intervention, Mechanical ventilation, Intensive care unit Background increase in PPCI volume and a reduction in hospital Acute myocardial infarction, in particular ST-segment mortality associated with STEMI [2, 3]. A major driver elevation myocardial infarction (STEMI) remains a time- to facilitate this has been the creation and implementa- sensitive medical emergency associated with significant tion of organised PPCI networks that are able to triage morbidity and mortality [1]. In recent years, the wide- and deliver patients directly to centres able to routinely spread recognition of primary percutaneous coronary provide this service both in- and out-of-hours [4, 5]. intervention (PPCI) as an evidence-based treatment Patients are subsequently generally cared for in a strategy that can improve outcomes has led to both an coronary-care unit (CCU), which has been shown to reduce mortality [6]. * Correspondence: ken.parhar@albertahealthservices.ca The National Infarct Angioplasty Project has demon- Department of Anesthesia and Intensive Care, Papworth Hospital, strated the benefits of PPCI over thrombolysis for treat- Cambridge, England 3 ment of STEMI patients [7] and has led to the creation Department of Critical Care Medicine, University of Calgary, ICU Administration - Ground Floor - McCaig Tower, Foothills Medical Center, of PPCI centres across England. By 2013, some regions 3134 Hospital Drive NW, Calgary, AB T2N 5A1, Canada demonstrated that more than 95% of patients treated for Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Parhar et al. Journal of Intensive Care (2018) 6:5 Page 2 of 10 STEMI received PPCI, compared with only 30% in the local database (Philips CVIS, Netherlands), routinely third quarter of 2008 [5]. collected for national audits, and patient case-notes Despite the pervasiveness of PPCI in the management where appropriate. ICU interventions, length of stay, of STEMI and the appropriate use of CCU care, there and complications were extracted from CIS. Survival remains a small proportion of patients that become data including the ICU and 28 day/hospital outcome critically ill and require advanced life support modalities was derived from both CIS, case notes and local data- post-PPCI, such as mechanical ventilation or vasoactive bases linked to national outcome data. therapy that may only be provided within the intensive Vital signs on admission (including heart rate, blood pres- care unit (ICU). Historically, patients with a complicated sure and mean arterial pressure) are reported as mean over myocardial infarction requiring mechanical ventilation the first 24 h of ICU admission. The admission PaO2 to have been associated with high rates of morbidity and FiO2 (PF) ratio, creatinine, platelets, bilirubin were the mortality [8–13]. worst value measured over the first 24 h. Pulmonary edema Patients that may require ICU post-PPCI remain was defined as hypoxemia with associated radiographic poorly defined. This retrospective single-centre cohort evidence of interstitial and/or alveolar edema. Cardiogenic review aims to describe the incidence of admission to shock was defined as a systolic blood pressure < 90 mmHg ICU, indication for ICU admission, and quantify the with clinical evidence of hypoperfusion (cyanosis, mottling, morbidity and mortality associated with ICU admission. oliguria, cold extremities) or the requirement for an In addition, factors associated with survival are assessed. inotrope. New onset renal dysfunction was defined as a 25% rise in serum creatinine or the requirement for renal Methods replacement therapy. The initiation of renal replacement Patient population therapy was based on refractory hyperkalemia, refractory We undertook a retrospective review of all consecutive acidosis, or volume overload despite medical management. patients admitted to a single tertiary cardiothoracic ICU Major hemorrhage was clinical evidence of bleeding with post-PPCI between January 2009 and May 2014. The the requirement for four or more units of red blood cells. unit is the sole provider of intensive care in a subspe- Infection was a positive culture result, or clinical syndrome cialty cardiothoracic hospital serving an English region consistent with infection such as pneumonia (fever, elevated with a catchment area of approximately three million. white cell count, purulent sputum, hypoxemia). Sequential All patients requiring PPCI in this region are transferred organ function failure assessment (SOFA) score was calcu- to this institution. lated as previously described [14, 15]. The search was performed via the electronic Clinical Information System (CIS), which maintains the elec- Groups tronic medical record of all patients admitted to ICU. Patient outcomes were analysed based on ICU survival. The initial search yielded 191 patients. Patients were Patient were stratified and analysed based on one of four excluded if not admitted directly post-PPCI. Ninety indications for ICU admission including out-of-hospital patients were excluded including: patients admitted cardiac arrest (OHCA), in-hospital cardiac arrest (IHCA), immediately before or after cardiac surgery or cardiac cardiogenic shock, or pulmonary edema. IHCA was procedures other than PPCI (n = 78), post respiratory defined as a cardiac arrest occurring following arrival to medicine procedures (n = 2), patients admitted due to hospital (most commonly during cardiac catheterization), lack of beds in CCU (n = 9), and patients admitted for but prior to admission to ICU. Cardiac arrests occurring end of life care (n = 1). A total of 101 patients post-PPCI while in ICU were listed as an ICU complication. were appropriate for detailed chart review and analysis (Fig. 1). Statistical analysis Clinical data The Shapiro-Wilks test for normality was performed on Demographic data (including age, gender, past medical all continuous variables. Continuous variables with normal history, and cardiovascular risk factors) were extracted distribution were reported as means with standard devi- from case-notes and the electronic CIS. Baseline physio- ation and analysed by unpaired student’s two-tailed t test logical characteristics (vital signs, Glasgow coma scale or one-way analysis of variance (ANOVA) where appro- (GCS), laboratory values) were extracted from the priate. Non-normally-distributed data were reported as electronic CIS. Details related to PPCI admission, echo- median with interquartile range and analysed with the cardiograms, and cardiac catheterization (downtime, Mann-Whitney U test or the Kruskal-Wallis test where location of infarction, procedures performed, anatomy of appropriate. Categorical variables were analysed with the coronary disease, complications, door-to-balloon time, chi-squared test or Fisher’s exact test where appropriate. pre-PCI interventions) were extracted from a dedicated A p value of < 0.05 was considered statistically significant. Parhar et al. Journal of Intensive Care (2018) 6:5 Page 3 of 10 Fig. 1 Flowchart outlining patient selection Variables that were statistically significant in the uni- Of the 101 patients who were admitted to ICU, the variate analysis (with a p value < 0.10) were considered majority were male (69%), with a mean age of 65 years for inclusion in the multivariable logistic regression (Table 1). Out of hospital cardiac arrest (OHCA) was the model. ICU mortality was defined as the dependant most common indication for admission to ICU (36.6%). A variable. Backward stepwise variable elimination was significant proportion of patients were admitted for in- performed (with a variable exit threshold set at p > 0.05). hospital cardiac arrest (IHCA; 31.7%) and cardiogenic The performance of the final model was assessed using shock (22.8%). The least common indication for admission the area under the receiver-operating characteristic to ICU post-PPCI was pulmonary edema (8.9%). Overall (AUROC) curve. ICU mortality was 33.7% for the entire cohort. Statistical analysis was performed using Stata Version Univariate factors that demonstrated a statistically signifi- 13.1 (StataCorp, USA). cant difference between survivors and non-survivors included age, low blood pressure on admission (both Ethics systolic and mean arterial pressure), low PF ratio, low GCS, Ethical approval was obtained from the Papworth Hospital high creatinine, and high SOFA scores. In the subgroup of NHS Foundation Trust research and development board patients suffering from an OHCA, downtime before return for the completion of this study. of spontaneous circulation (ROSC) was statistically differ- ent between survivors and non-survivors. Survivors of ICU Results post PPCI were associated with a shorter downtime in One-hundred one patients met the inclusion criteria for comparison to non-survivors (Fig. 2). Patients who suffered this retrospective observational study (Fig. 1). During awitnessed IHCA didnot demonstrate a difference in time this time, a total of 2902 PPCI were performed, resulting to ROSC between survivors and non-survivors. When in a post-PPCI incidence of admission to ICU post PPCI patients were stratified based on their indication for admis- of 3.5%. sion (OHCA, IHCA, shock, or pulmonary edema) to ICU Parhar et al. Journal of Intensive Care (2018) 6:5 Page 4 of 10 Table 1 Patient demographic factors for patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All patients Outcome Indication for ICU Survivor Non-survivor Sign OHCA IHCA Card shock Pulm edema Sign Total no of patients (%) 101 (100) 67 (66.3) 34 (33.7) 37 (36.6) 32 (31.7) 23 (22.8) 9 (8.9) Gender Male, no (%) 70 (69.3) 48 (47.5) 22 (21.8) 0.500 29 (28.7) 20 (19.8) 15 (14.9) 6 (5.9) 0.505 Age, years 65.3 (12.8) 63.8 (11.5) 68.3 (14.8) 0.047 60.2 (12.8) 66.8 (12.6) 71.2 (10.7) 66.0 (11.8) 0.009 Cardiovascular risk factors Smoking, no (%) 28 (27.7) 19 (18.8) 9 (8.91) 1.000 11 (10.9) 11 (10.9) 3 (3.0) 3 (3.0) 0.335 Diabetes mellitus, no (%) 21 (20.8) 10 (9.9) 11(10.9) 0.067 4 (4.0) 7 (6.9) 8 (7.9) 2 (2.0) 0.171 Dyslipidaemia, no (%) 30 (29.7) 22 (21.8) 8 (7.9) 0.367 8 (7.9) 10 (9.9) 9 (8.9) 3 (3.0) 0.526 Hypertension, no (%) 58 (57.4) 40 (39.6) 18 (17.8) 0.531 18 (17.8) 17 (16.8) 16 (15.8) 7 (6.9) 0.229 Past medical history Previous MI, no (%) 20 (19.8) 15 (14.9) 5 (5.0) 0.436 3 (3.0) 4 (4.0) 8 (7.9) 5 (5.0) 0.002 Previous CAD, no (%) 29 (28.7) 21 (20.8) 8 (7.9) 0.490 4 (4.0) 9 (8.9) 10 (9.9) 6 (5.9) 0.002 Previous CHF, no (%) 3 (3.0) 2 (2.0) 1 (1.0) 1.000 0 (0.0) 1 (1.0) 1 (1.0) 1 (1.0) 0.340 Renal failure, no (%) 12 (11.9) 8 (7.9) 4 (4.0) 1.000 3 (3.0) 2 (2.0) 5 (5.0) 2 (2.0) 0.210 COPD no, no (%) 11 (10.9) 9 (8.9) 2 (2.0) 0.326 3 (3.0) 6 (5.9) 0 (0.0) 2 (2.0) 0.096 Baseline characteristics on admission HR (bpm) 79.7 (15.6) 78.5 (16.0) 82.0 (14.5) 0.297 70.6 (15) 80.4 (12.3) 87.8 (13.4) 93.8 (11.7) < 0.001 Systolic BP (mmHg) 106.8 (19.5) 111.8 (17.9) 96.3 (18.7) < 0.001 106.9 (16.4) 103.16 (20.7) 108.9 (21.2) 114.0 (22.2) 0.462 MAP (mmHg) 73.0 (13.0) 77.7 (10.3) 63.7 (12.9) < 0.001 72.5 (12.4) 73.7 (15.3) 71.4 (9.5) 77.0 (15.0) 0.720 PaO2/FiO2 ratio, med (IQR) 143 (98–233) 154 (98–271) 105 (83–173) 0.036 157.9 (105–241) 165 (83–286) 105 (83–143) 128 (75–278) 0.138 GCS, med (IQR) 3 (3–15) 11 (3–15) 3 (3–3) < 0.001 3 (3–4) 3 (3–14.5) 14 (3–15) 3 (3–15) 0.071 Serum creatinine (μmol/L), med (IQR) 116 (87–157) 102 (84–129) 156 (115–203) < 0.001 101 (71–126) 116 (95–155) 140 (112–191) 135 (117–144) 0.012 SOFA score 8.4 (3.3) 7.4 (2.9) 10.4 (3.1) < 0.001 8.6 (2.6) 8.5 (3.5) 8.3 (3.4) 8.0 (5.2) 0.953 Indication for ICU admission OHCA, no (%) 37 (36.6) 26 (25.7) 11 (10.9) 0.663 Downtime before ROSC (min), (IQR) 20 (15–30) 15 (10–20) 35 (30–40) < 0.001 IHCA, no (%) 32 (31.7) 19 (18.8) 13 (12.7) 0.368 Downtime before ROSC (min), (IQR) 10 (5–20) 9 (5–14) 15 (5–42) 0.214 Cardiogenic shock, no (%) 23 (22.8) 14 (13.9) 9 (8.9) 0.617 Acute pulmonary oedema, no (%) 9 (8.9) 8 (7.9) 1 (1.0) 0.266 post PPCI, there was no difference in mortality amongst with reduced survival included severe LV dysfunction, right the four groups. ventricle (RV) involvement, and the need for intra-aortic STEMI was the most common type of presenting balloon pump (IABP) insertion in the cath lab. The indica- acute coronary syndrome (91%) (Table 2). Other patients tions for IABP insertion in the cath lab included cardio- who underwent PPCI had either indeterminate ACS genic shock, bridge for high risk PCI, and ongoing chest (due to a left bundle branch block) or a high suspicion pain. IABP were all inserted prior to admission to ICU. The of an evolving transmural infarct. The majority were in cardiologic factors did not influence the indication for the anterior territory (61%) and uncommonly involved admission to ICU (Additional file 1:Table S1). the right ventricle (5.0%). Left ventricular (LV) systolic The median duration of stay in the ICU was 3 days function was depressed in the majority of patients with (Table 3). Most patients required invasive mechanical over 50% of patients having either moderate or severe ventilation (IMV) (86.1%) with median duration of IMV LV dysfunction as determined by echocardiography dur- being 2 days. The majority of the mortality occurred ing admission. Only one patient received thrombolytics within the ICU (34 of 37 patients). Significant complica- prior to PPCI. Angiogram was successfully performed in tions were common with patients suffering major bleeding the majority of patients (98.0%) with the exception of (9.9%), infections (31.7%), acute kidney injury (33.7%), or two patients in whom it was attempted but aborted due in ICU cardiac arrest (6.9%). Factors that statistically asso- to cardiac arrest. There was a high rate of PCI per- ciated with reduced survival included the lack of use of formed (90.1%). Factors that were statistically associated non-invasive ventilation (NIV), inotropes and vasopressor Parhar et al. Journal of Intensive Care (2018) 6:5 Page 5 of 10 Fig. 2 Box and whisker plots of the effect of downtime on return of spontaneous circulation in OHCA patients Table 2 Cardiac characteristics of patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All Patients Outcome Survivor Non-survivor Sign Total number of patients (%) 101 (100) 67 (66.3) 34 (33.7) STEMI, no (%) 91 (90.1) 58 (57.4) 33 (32.7) 0.158 MI territory Anterior, no (%) 61 (61.0) 42 (42.0) 19 (19.0) 0.667 Inferior, no (%) 38 (38.0) 26 (26.0) 12 (12.0) 1.000 Lateral, no (%) 32 (32.0) 22 (22.0) 10 (10.0) 1.000 RV involvement, no (%) 5 (5.0) 1 (1.0) 4 (4.0) 0.040 Peak troponin, ng/L med (IQR) 38.9 (13.7–40.0) 26.8 (10.9–40.0) 40.0 (19.1–626.0) 0.146 LV systolic function Normal, no (%) 10 (11.6) 8 (9.3) 2 (2.3) 0.488 Mild dysfunction, no (%) 26 (30.2) 21 (24.4) 5 (5.8) 0.093 Moderate dysfunction, no (%) 22 (25.6) 17 (19.8) 5 (5.8) 0.309 Severe dysfunction, no (%) 28 (32.6) 14 (16.3) 14 (16.3) 0.037 Thrombolysis pre-PPCI, no (%) 1 (1.0) 1 (1.0) 0 (0.0) 1.000 Angiogram, (successful completion) no (%) 99 (98.0) 67 (66.3) 32 (31.7) 0.111 PCI performed (successful completion), no (%) 91 (90.1) 62 (61.4) 29 (28.7) 0.298 IABP in cath lab, no (%) 50 (49.5) 28 (27.7) 22 (21.8) 0.036 Number of diseased vessels, med (IQR) 2 (1–3) 2 (1–3) 2 (2–3) 0.514 Left main stem disease, no (%) 14 (14.1) 8 (8.1) 6 (6.1) 0.371 TIMI flow, med (IQR) 3 (2–3) 3 (2–3) 3 (2–3) 0.862 Symptom onset to device time (min, med (IQR) 210 (155–332) 219 (159–328) 200 (150–350) 0.665 Parhar et al. Journal of Intensive Care (2018) 6:5 Page 6 of 10 Table 3 Intensive care characteristics and complications of patients admitted to ICU post PPCI. Results are expressed as mean (SD) unless otherwise denoted All Outcome Indication for ICU patients Survivor Non-survivor Sign OHCA IHCA Card shock Pulm edema Sign Total number of patients (%) 101 (100) 67 (66.3) 34 (33.7) 37 (36.6) 32 (31.7) 23 (22.8) 9 (8.9) ICU interventions Invasive mechanical ventilation, no (%) 87 (86.1) 56 (55.5) 31 (30.7) 0.373 37 (36.6) 31 (30.7) 12 (11.9) 7 (6.9) < 0.001 Duration of IMV, median days (IQR) 2 (1–3) 2 (1–2) 2 (1–6) 0.314 2 (2–4) 1 (1–2) 2 (1–5) 1 (1–1) 0.011 Non-invasive ventilation, no (%) 25 (24.8) 21 (20.8) 4 (4.0) 0.049 7 (6.9) 5 (5.0) 8 (7.9) 5 (5.0) 0.047 Duration of NIV, median days (IQR) 1 (1–2) 1 (1–2) 2.5 (1.5–3) 0.075 1 (1–1) 2 (1–2) 2 (1.5–3) 1 (1–1) 0.032 Inotropes, median number (IQR) 1 (0–1) 0 (0–1) 1 (0–2) 0.005 1 (0–1) 1 (0–2) 0 (0–1) 0 (0–1) 0.617 Vasopressors, median number (IQR) 0 (0–1) 0 (0–1) 1 (0–1) 0.001 0 (0–1) 0 (0–1) 0 (0–1) 0 (0–1) 0.971 ECMO, no (%) 7 (6.9) 1 (1.0) 6 (5.9) 0.006 0 (0.0) 7 (6.9) 0 (0.0) 0 (0.0) 0.001 Therapeutic hypothermia, no (%) 48 (47.5) 33 (32.7) 15 (14.9) 0.677 32 (31.7) 14 (13.9) 0 (0.0) 2 (2.0) < 0.001 IABP, no (%) 59 (58.4) 35 (34.7) 24 (23.8) 0.090 15 (14.9) 23 (22.8) 18 (17.8) 3 (3.0) 0.004 Renal repl therapy, no (%) 27 (26.7) 10 (9.9) 17 (16.8) < 0.001 6 (5.9) 11 (10.9) 8 (7.9) 2 (2.0) 0.273 In-hospital complications Major bleeding, no (%) 10 (9.9) 6 (5.9) 4 (4.0) 0.082 0 (0.0) 7 (6.9) 2 (2.0) 1 (1.0) 0.026 Infections, no (%) 32 (31.7) 21 (20.8) 11 (10.9) 1.000 13 (12.9) 9 (8.9) 7 (6.9) 3 (3.0) 0.936 Renal dysfunction (new onset), no (%) 34 (33.7) 18 (17.8) 16 (15.8) 0.048 12 (11.9) 11 (10.9) 9 (8.9) 2 (2.0) 0.833 In ICU Cardiopulmonary arrest, no (%) 7 (6.9) 0 (0.0) 7 (6.9) < 0.001 3 (3.0) 4 (4.0) 0 (0.0) 0 (0.0) 0.261 Outcomes Duration of ICU stay, median days (IQR) 3 (1–5) 3 (1–4) 2 (0.5–7) 0.389 3 (2–7) 2 (1–5) 3 (0.5–5) 1 (0.5–2) 0.095 ICU mortality, no (%) 34 (33.7) 11 (10.9) 13 (12.9) 9 (8.9) 1 (1.0) 0.346 Hospital / 28-day mortality, no (%) 37 (36.6) 12 (11.9) 14 (13.9) 10 (9.9) 1 (1.0) 0.265 Cause of death (of 37 patients) Treatment withdrawn, no (%) 25 (67.6) 7 (18.9) 9 (24.3) 8 (21.6) 1 (2.7) 0.632 Cardiac Arrest, no (%) 7 (18.9) 3 (8.1) 2 (5.4) 2 (5.4) 0 (0.0) 0.867 Other 5 (13.5) 2 (5.4) 3 (8.1) 0 (0.0) 0 (0.0) 0.463 use, transfusion of blood products including red blood cells in multivariable regression analysis. Factors that were in- (RBCs) and nonRBCs, as well as need for extracorporeal dependently associated with ICU mortality included high membrane oxygenation (ECMO) or renal replacement SOFA score and pre-ICU insertion of an IABP (Table 4). therapy (RRT). ECMO was used exclusively in patients who Notable factors that were not independently associate with sufferedIHCAatany pointduringthe ICUadmission. mortality included age, presence of RV dysfunction, and Therapeutic hypothermia was used in patients who suffered presence of severe LV dysfunction. The odds ratio (OR) either OHCA or IHCA in patients with an initial rhythm of for increased mortality for each point increase in SOFA ventricular tachycardia or ventricular fibrillation, but was was 1.43 (95% CI 1.2–1.7). The OR for increased mortality not associated with a statistically significant increase in when an IABP was inserted pre-ICU admission (during survival. There were higher than expected rates of bleeding cardiac catheterization) was 3.38 (95% CI 1.27–9.03). The and transfusions (RBC) in the IHCA group. sensitivity and specificity of this model was 50 and 91% Twenty-eight-day mortality was similar to ICU mortality respectively with a positive predictive value (PPV) of 73.9% (Table 3, 36.6 vs 33.7%). The cause of death in most patients was withdrawal of care (67.6%). Post ICU admis- Table 4 Multivariable logistic regression analysis of factors sion cardiac arrest occurred in seven patients (18.9%), none associated with ICU mortality of whom survived. Odds ratio Standard error zP value 95% CI Pre-ICU admission factors that demonstrated a statisti- SOFA 1.43 0.127 4.01 0.000 1.200–1.700 cally significant difference between survivors and non- IABP 3.38 1.695 2.43 0.015 1.266–9.030 survivors in univariate analysis were selected for inclusion Parhar et al. Journal of Intensive Care (2018) 6:5 Page 7 of 10 and a negative predictive value (NPV) of 78.2%. This model shock following complicated myocardial infarction, our correctly classified 77.2% of patients in this series and had study reviewed consecutive patients admitted to ICU an AUROC curve of 0.7842 (Fig. 3). When using a model exclusively via the PPCI pathway [8–13, 16, 17]. This with only SOFA and without IABP, the AUROC was included both patients who required mechanical ventila- slightly lower (0.75 CI 0.65–0.85) in comparison to tion and those who did not. the model with SOFA and IABP (0.78 CI 0.68–0.89). A higher SOFA score was associated with increased mortality (Table 4). This suggests that degree of organ Discussion dysfunction in patients with complicated myocardial In this retrospective observational study, we present a infarction, as with many other critical illnesses, is a series of consecutive patients post-PPCI pathway that major determinant of survival. Surprisingly, neither the are critically ill and require admission to the ICU for requirement for mechanical ventilation nor the indica- advanced therapies that may only be provided in ICU tion for admission were independently associated with such as invasive mechanical ventilation or vasoactive mortality. To date, no study has described this relation- support. There is a significant mortality amongst these ship exclusively in the post-PPCI patient population. A patients (33.6%), which is significantly higher than the previous study looking at traditional risks scores used in general PPCI population. Indication for admission the myocardial infarction population such as the Global (cardiac arrest, pulmonary edema, cardiogenic shock) Registry of Acute Coronary Events (GRACE) risk score does not statistically influence mortality and all groups or the Thrombolysis in Myocardial Infarction (TIMI) were similar despite their indication. Those patients risk score in comparison with SOFA demonstrated that presenting with higher SOFA scores (reflecting a higher SOFA provided reasonable discrimination of prognosis degree of multiple-organ dysfunction), or requiring an [18]. This study was limited, as it did not focus on the IABP during cardiac catheterization were independently post-PPCI population or those patients specifically who associated with higher mortality. were admitted to ICU, which are most likely to be critic- Despite an era of appropriate anti-ischemic therapy ally ill and potentially benefit from prognostication. Our post-STEMI and provision of organised and timely study is novel as we demonstrate that the SOFA score reperfusion via PPCI, there remain a proportion of does predict mortality in this high-risk group of patients patients who become critically ill and require admission admitted to the ICU who require mechanical ventilation to ICU for invasive monitoring, mechanical ventilation and vasopressors. Previous studies looking specifically at or vasoactive therapy. Patient mortality in this group patients admitted to ICU with cardiogenic shock demon- remains high despite improving outcome for all patients strated that there was an association between scores such with STEMI presenting for PPCI [3]. as Acute Physiology and Chronic Health II/III (APACHE In contrast to previous studies of patients requiring II/III), Simplified Acute Physiology Score II (SAPSII), mechanical ventilation or suffering from cardiogenic SOFA and survival outcome [16, 17]. The specific organ Fig. 3 Area under the receiver operating curver (AUROC) of multivariable logistic regression model using IABP and SOFA Parhar et al. Journal of Intensive Care (2018) 6:5 Page 8 of 10 systems within the SOFA score that were responsible for (E-CPR). The IHCA group had a high rate of major the higher scores included increased renal dysfunction, bleeding most likely associated with the use of E-CPR, lower admission GCS, as well as worse hypoxemia (lower as this association is a well described in other ECMO PaO2/FiO2 ratio (Table 1). The benefit of using SOFA populations [26]. Survival in this group was low which is scores and the presence or absence of IABP to prognosti- consistent with previously published reviews on the use cate patients is that it can be easily calculated upon admis- of E-CPR in this age demographic [27]. sion to ICU with information routinely available. This is This study had several limitations. It was performed at the drawback of scores such as APACHE II/III and SAPSII a single tertiary PPCI referral centre and is retrospective as they are more complex and time consuming to calcu- in nature and thus data collection was based on review late when compared to SOFA [19]. SOFA was used as a of the CIS and paper charts. The multivariable logistic prognostic score due to its simplicity and ability to be regression model was not externally validated in an calculated with very routine and objective patient data. alternate population or in patients not admitted to ICU. Retrospective data collection made it difficult to use alter- Furthermore, there may be selection bias for patients nate scores such as APACHE II due to the high number requiring mechanical circulatory support with IABP due of variables required in these scores including patient to differences in individual clinical practice patterns. historical factors and the risk of missing data [19]. For This study provides a rationale for a future prospective example, any missing data precluded patients from being observational study and validation of the multivariable included in APACHE II score calculation as per the model to determine if this may help triage and prognos- original description of APACHE II [20]. In addition, it has ticate patients who are not likely to survive post compli- been demonstrated that there are significant differences in cated acute myocardial infarction. Potential uses for this the ability of APACHE II to be calculated accurately when type of model include being able to provide prognostic comparing prospective and retrospective collection of data information for care providers and patient family [21]. This further highlights the strength of the SOFA members. It may also help identify patients in whom score as it is quick and easy to calculate using commonly aggressive care may be deemed unlikely to succeed. available objective clinical data. Alternatively, if these patients are identified correctly a We demonstrated that use of IABP was independently priori, it may allow a targeted intervention to improve associated with mortality which is in keeping with previ- outcomes in this cohort of patients who continue to ously reported observational data [22, 23]. The cohort of have an extremely poor outcome. the study patients who required mechanical circulatory support with IABP and ICU admission was representa- Conclusions tive of the higher risk patient population and therefore Despite only requiring admission 3.5% of the time to IABP support may have been given to the sicker patients ICU (101 of 2902 patients), those patients suffering an which would induce bias towards poor outcomes in that MI that do require ICU post PPCI are very critically ill group. A meta-analysis of cohort studies in the context and have a mortality of 33.7%. The most effective way to of STEMI leading to cardiogenic shock supported the prognosticate survival in this cohort of patients is by use of IABP adjunctive to fibrinolysis [24]. It remains using the SOFA score, in addition to the requirement unknown whether early IABP placement can improve for an intra-aortic balloon pump. clinically important outcomes in patients with STEMI requiring ICU admission. In the subgroup of patients with an OHCA, a longer Additional file down time before ROSC was associated with higher Additional file 1: Table S1. Cardiac characteristics of patients admitted mortality; however, in the multivariable analysis, this was to ICU post PPCI by indication. Results are expressed as mean (SD) unless not an independent predictor for increased mortality. otherwise denoted. (DOCX 17 kb) The association between prompt ROSC and outcome has been well described previously [25]. Similarly age Abbreviations was a univariate factor associated with increased mortal- ANOVA: Analysis of variance; APACHE: Acute physiology and chronic health; ity however was not an independent predictor in the AUROC: Area under the receiver operating curve; CAD: Coronary artery disease; multivariable analysis. It may be that increased age and CCU: Coronary care unit; CIS: Clinical information system; ECMO: Extracorporeal membrane oxygenation; E-CPR: Ecmo during cardio-pulmonary resuscitation; longer downtimes before ROSC are all reflective of GCS: Glasgow coma scale; IABP: Intra-aortic balloon pump; ICU: Intensive care increased likelihood of organ dysfunction and a higher unit; IHCA: In-hospital cardiac arrest; IMV: Invasive mechanical ventilation; SOFA score, thus not independently associated with LV: Left ventricle; NIV: Non-invasive mechanical ventilation; NPV: Negative predictive value; OHCA: Out of hospital cardiac arrest; OR: Odds ratio; mortality. PF: PaO2:FiO2; PPCI: Primary percutaneous coronary intervention; PPV: Positive In the IHCA group, there were five patients who were predictive value; RBC: Red blood cells; ROSC: Return of spontaneous circulation; supported with ECMO under cardiac arrest conditions RRT: Renal replacement therapy; RV: Right ventricle; SAPSII: Simplified acute Parhar et al. Journal of Intensive Care (2018) 6:5 Page 9 of 10 physiology score II; SOFA: Sequential organ failure assessment; STEMI: ST-segment 6. Rotstein Z, Mandelzweig L, Lavi B, Eldar M, Gottlieb S, Hod H. Does the elevation myocardial infarction coronary care unit improve prognosis of patients with acute myocardial infarction? A thrombolytic era study. Eur Heart J. 1999;20:813–8. 7. McLenachan JM, Gray HH, de Belder MA, Ludman PF, Cunningham D, Acknowledgements Birkhead J. Developing primary PCI as a national reperfusion strategy for Thank Dr. Dan Niven with advice on statistical analysis with this manuscript. patients with ST-elevation myocardial infarction: the UK experience. EuroIntervention. 2012;8(Suppl P):P99–107. Funding 8. Ariza Sole A, Salazar-Mendiguchia J, Lorente-Tordera V, Sanchez-Salado JC, This research did not receive any specific grant from funding agencies in the Gonzalez-Costello J, Moliner-Borja P, Gomez-Hospital JA, Manito-Lorite N, public, commercial, or not-for-profit sectors. Cequier-Fillat A. Invasive mechanical ventilation in acute coronary syndromes in the era of percutaneous coronary intervention. Eur Heart J Availability of data and materials Acute Cardiovasc Care. 2013;2:109–17. The datasets generated and/or analysed during the current study are not 9. Lopez Messa JB, Andres De Llano JM, Berrocal De La Fuente CA, Pascual publicly available due to privacy and ethics compliance but are available Palacin R, Analisis Retraso Infarto Agudo M. Characteristics of acute from the corresponding author on reasonable request. myocardial infarction patients treated with mechanical ventilation. Data from the ARIAM registry. Rev Esp Cardiol. 2001;54:851–9. Author’s contributions 10. Kouraki K, Schneider S, Uebis R, Tebbe U, Klein HH, Janssens U, Zahn R, KP, KJ, VM, EB, and VZ contributed to data collection. KP, VZ, NW, and AV were Senges J, Zeymer U. Characteristics and clinical outcome of 458 patients involved in the study design, statistical methodology, interpretation of results, and with acute myocardial infarction requiring mechanical ventilation. Results of writing of the manuscript. All authors read and approved the final manuscript. the BEAT registry of the ALKK-study group. Clin Res Cardiol. 2011;100:235–9. 11. Zahger D, Maimon N, Novack V, Wolak A, Friger M, Gilutz H, Ilia R, Almog Y. Ethics approval and consent to participate Clinical characteristics and prognostic factors in patients with complicated Ethical approval was obtained from the Papworth Hospital NHS Foundation acute coronary syndromes requiring prolonged mechanical ventilation. Am Trust research and development board for the completion of this study. J Cardiol. 2005;96:1644–8. 12. Lesage A, Ramakers M, Daubin C, Verrier V, Beynier D, Charbonneau P, du Cheyron D. Complicated acute myocardial infarction requiring mechanical Consent for publication ventilation in the intensive care unit: prognostic factors of clinical outcome Not applicable in a series of 157 patients. Crit Care Med. 2004;32:100–5. 13. Eran O, Novack V, Gilutz H, Zahger D. Comparison of thrombolysis in Competing interests myocardial infarction, global registry of acute coronary events, and acute The authors declare that they have no competing interests. physiology and chronic health evaluation II risk scores in patients with acute myocardial infarction who require mechanical ventilation for more than 24 hours. Am J Cardiol. 2011;107:343–6. Publisher’sNote 14. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Springer Nature remains neutral with regard to jurisdictional claims in Reinhart CK, Suter PM, Thijs LG. The SOFA (sepsis-related organ failure published maps and institutional affiliations. assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Author details Intensive Care Medicine. Intensive Care Med. 1996;22:707–10. Department of Anesthesia and Intensive Care, Papworth Hospital, 15. 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Journal of Intensive CareSpringer Journals

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