Prediction of requirement for, and outcome of, prolonged mechanical ventilation following cardiac surgery

PII: S0967-2109(97)00024-0

Cardiovascular Surgery, Vol. 5, No. 4, pp. 376–381, 1997  1997 The International Society for Cardiovascular Surgery Published by Elsevier Science Ltd. Printed in Great Britain 0967–2109/97 $17.00 + 0.00

Prediction of requirement for, and outcome of, prolonged mechanical ventilation following cardiac surgery M. J. Thompson*, R. A. Elton†, P. A. Mankad*, C. Campanella*, W. S. Walker*, C. T. M. Sang* and E. W. J. Cameron* *Department of Cardiothoracic Surgery, Royal Infirmary, Lauriston Place, Edinburgh, EH3 9YW, UK and †Medical Statistics Unit, University of Edinburgh, Teviot Place, Edinburgh, UK The prediction of requirement for, and short- and long-term outcome of, prolonged mechanical ventilation after cardiac surgery is ill-defined. The aims of this study were to isolate any predictive indices which might identify those groups of patients who may require prolonged ventilation postoperatively and to determine which factors significantly affect outcome in the prolonged-ventilation group. Following case note review of 139 consecutive cardiac surgical patients ventilated for ⭓ 7 days following surgery, 43 factors were recorded on each patient, including smoking, pulmonary function, chest infection, and chronic obstructive airways disease. Of 139 patients, 89 were discharged from hospital (64% survival); of these, 52 were alive at long-term follow-up (58% long-term survival). Statistical analysis identified urban residence, chronic obstructive airways disease, prolonged operation, and bypass time as significant predictors of requirement for prolonged ventilation postoperatively. On multivariate analysis five factors were predictive of increased intensive care mortality, including urban residence, inotrope days, sepsis, perioperative cerebrovascular accident and coagulopathy requiring fresh frozen plasma transfusion postoperatively. Following discharge from hospital, four factors were found to be significant predictors of increased mortality: these are impaired preoperative ejection fraction, increasing age, impaired preoperative pulmonary function, and abscence of preoperative aspirin medication. These factors should be considered in intensive care planning, long-term follow-up and importantly on clinical decision making in the individual patient.  The International Society for Cardiovascular Surgery Keywords: cardiac surgery, mechanical ventilation, statistical analysis, multivariate analysis, planning, follow-up

In the increasing trend towards minimizing intensive care stay and facilities for patients following openheart surgery [1, 2], there remains a group of patients who require continued intensive care because of ventilator dependency. Although the majority of patients in intensive care are ventilated for less than 1 day this study concentrates on the ‘problem’ group of patients who remain ventilated 1

Correspondence to: Miss M. J. Thompson

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week after surgery. Previous data have shown that mortality increases significantly in patients staying ⭓ 7 days in the ICU after cardiac surgery [3]. Furthermore, studies on intensive care cardiac surgical patients have revealed that being intubated and unable to talk are perceived as the two most stressful perioperative events [4]. Little data exist concerning the associated mortality of patients requiring prolonged mechanical ventilation beyond 6 days after cardiac surgery. Kollef et al. [5] studied a group who were still ventilated after only 48 hours. An organ system failure index CARDIOVASCULAR SURGERY

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of ⭓ 3 was identified as being associated with increased ICU mortality. A study by Durand et al. [6] of factors which contributed to a requirement for prolonged ventilation determined that preoperative pulmonary function tests were effective in predicting such need in cardiac surgical patients. Dias et al. [7] identified five preoperative factors and six postoperative factors associated with increased mortality following mechanical ventilation over 24 hours. These, plus others, are re-examined in this study. Studies in general intensive care have indicated that age has an important impact on outcome following prolonged ventilation [8] and that the elderly experience more complications and a higher mortality [9]; moreover, their survival is less cost-effective than in younger patients [10]. However, it has also been established that other factors such as ICU stay duration and diagnosis significantly affect outcome, and age in itself should not be used as an exclusion to prolonged ventilation [8]. The aims of this study were: (i) to further discern factors predictive of the need for prolonged mechanical ventilation following open-heart surgery; (ii) to determine intensive care and long-term survival in prolonged ventilation patients; (iii) to isolate factors predictive of increased intensive care mortality in the prolonged mechanical ventilation group; and (iv) to establish any factors predictive of increased longterm mortality in these patients.

Patients and methods Patients In the Edinburgh cardiac surgery centre, 4972 patients underwent open-heart surgery (including thoracic aortic surgery) between 1987 and 1992. Of these, 139 (2.8%) required postoperative mechanical ventilation for ⭓ 7 days. Some 76 patients (55%) were male, and 63 (45%) were female. The mean patient age was 62 (range 24–79) years. A retrospective case note review was undertaken of the 139 patients documenting a total of 43 preoperative, intraoperative and postoperative factors as listed in Figure 1. In addition to general factors such as operation type, age, New York Heart Association (NYHA) status and Parsonnet score, data were collected on pulmonary function tests, smoking, bronchodilator, diuretic and other preoperative drugs, and also socioeconomic factors such as urban residence. Intraoperative factors analysed included bypass and cross-clamp times and details of myocardial revascularization. Postoperative factors analysed included duration of intensive care unit stay, requirement for reintubation, ventilator-associated pneumonia, tracheotomy and minitracheostomy, inotrope requirement CARDIOVASCULAR SURGERY

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and other postoperative complications. This information was entered onto an Excel 5 spreadsheet database. The general practitioners of the 103 intensive care survivors were contacted to establish whether or not their patients were still alive. In cases where this was not possible the referring cardiologist or area health board were contacted. The patients were subsequently contacted to confirm their survival status. Outcome was established in all survivors. Statistical analysis Statistical analysis was undertaken of pre- and intraoperative factors for determinants of requirement for prolonged ventilation using Chi-squared tests with Yates’ correction for binary factors, Wilcoxon ranksum tests for ordinal or quantitative factors, and Chisquared tests for nominal factors. For prediction of increased ICU mortality, univariate and multivariate analysis was undertaken. For predictors of increased out-of-hospital mortality, univariate and multivariate Cox regression analysis was undertaken.

Results The 139 patients who required mechanical ventilation for ⭓ 7 days had undergone the spectrum of operations listed in Table 1. Prediction of requirement for prolonged postoperative ventilation from preoperative and intraoperative factors analysed identified four factors of statistical significance. These are listed with their P values in Table 2 and are defined below: 1. Urban residence includes all patients from cities or towns in the five Scottish referral regions. 2. Preoperative chronic obstructive airways disease was defined as that already established and undergoing treatment before admission. 3. Operation time was the time from induction of anaesthesia until closure of skin and was documented from standardized anaesthetic charts. 4. Bypass time was the total sum of all episodes of cardiopulmonary bypass within a single operative procedure. Survival of the prolonged-ventilation patients was fully determined as it was possible to determine outcome in all 139 patients. Of this total population, 89 were discharged from the ICU and subsequently from hospital (64% ICU survival). In total, 37 patients died following hospital discharge, leaving 52 survivors at long-term follow-up (58%). Of the 43 factors analysed, 10 were found on univariate analysis to be predictors of increased intensive care mortality. These are listed with their P values in Table 3 and are further defined below. 377

Prolonged mechanical ventilation after cardiac surgery: M. J. Thompson et al.

General

Age Operation type Morbid obesity Operative priority Smoking Pulmonary function tests Chronic obstructive airways disease

Respiratory

PRE-OPERATIVE

NYHA grade Re-operation Parsonnet score Catastrophic states

Cardiac

Pharmacology

Steroids Diuretics Aspirin Bronchodilators All other drugs

Socioeconomic

Urban/rural residence

Surgical

Number of grafts Mammary used Length of operation Chest left open

Bypass

Bypass time Cross-clamp time

General

ITU Stay (days)

Cardiac

Inotrope days Intra-aortic ballon counterpulsation Arrhythmia Re-opening

INTRA-OPERATIVE

Respiratory

Reintubation Chest infection Pulmonary bacteria cultured Tracheostomy Minitracheostomy

Neurological

Cerebrovascular accident Confusional state

POST-OPERATIVE

Haematological

Surgical

Coagulopathy Fresh frozen plasma used

Other major operations Cardiac re-operation Sternal resuture

Figure 1 Factors analysed

1. Postoperative ‘inotrope days’ (1 inotrope day = cardiac inotrope × number of days administered (1 day ⱖ 12 h); inotropes include adrenaline, milrinone, isoprenaline, dobutamine and dopamine (ⱖ 5 µg/kg per min). 2. Sepsis included clinical diagnosis of sepsis requiring antibiotic or a strong growth (ⱖ 105 organisms/ml) on culture from any source. 3. Perioperative cerebrovascular accident – occurring intra- or postoperatively diagnosed clinically or on computed tomography scan. 378

4. Requirement for postoperative transfusion of ⭓ 1 U of fresh frozen plasma for coagulopathy. 5. Urban residence as previously detailed. 6. Noradrenaline – postoperative infusion as measured in days of requirement. 7. Postoperative intra-aortic balloon counterpulsation – measured in days of usage. 8. Postoperative confusional state – diagnosed clinically and requiring sedation. 9. Coagulopathy defined by abnormal clotting screen. CARDIOVASCULAR SURGERY

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Prolonged mechanical ventilation after cardiac surgery: M. J. Thompson et al. Table 1 Operative mix of patients requiring prolonged mechanical ventilation after cardiac surgery

Table 4 Factors predictive of increased ICU mortality in prolonged ventilation cardiac surgical patients (Multivariate analysis)

Operation

No. of patients

Factor

Coronary artery bypass grafting (CABG) Valve + CABG Aortic valve replacement (AVR) Aortic prosthetic replacement Mitral valve replacement (MVR) Mitral prosthetic replacement Mitral valve replacement + ASD Double valve replacement AVR, MVR, tricuspid annuloplasty MVR, tricuspid annuloplasty Replacement aortic root Aortic aneursym CABG + aortic aneurism CAGB + left ventricular aneursymectomy Ventricular septal defect (VSD) VSD + CABG Atrial septal defect (ASD) Total

48 17 8 12 12 10 1 1 1 1 1 1 1 1 1 12 1 139

Inotrope days Sepsis Urban residence Perioperative cerebrovascular accident Confusional state Fresh frozen plasma transfusion

P

Urban residence Operation duration Chronic obstructive airways disease Bypass time

⬍ ⬍ ⬍ ⬍

0.01 0.01 0.05 0.05

Table 3 Factors predictive of increased ICU mortality in cardiac surgical patients who require prolonged mechanical ventilation (Univariate analysis)

P

Factor Inotrope days Sepsis Perioperative cerebrovascular accident Fresh frozen plasma transfusion Urban residence Noradrenaline Intra-aortic balloon counterpulsation Acute confusional state Coagulopathy Sternal resuture

0.001 0.01 0.05 0.05 0.05 0.05

⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍

0.001 0.001 0.01 0.01 0.01 0.05 0.05 0.05 0.05 0.05

1. Impaired preoperative ejection fraction ⱕ 30% (as documented on cardiac catheterization). 2. Increasing age over the range 24 to 79 years. 3. Absence of preoperative prescribed aspirin. 4. Impaired preoperative pulmonary function tests FEV1/FVC expressed as a percentage of expected value (⬍ 70% = impaired).

Discussion This study isolated four factors predictive of increased requirement for prolonged mechanical ventilation following cardiac surgery, namely urban residence, chronic obstructive airways disease, operation duration, and bypass time. No data exist supporting urban residence as a predictor of increased ventilator requirement. However, Dias et al. [7] found that chronic obstructive pulmonary disease was associated with prolonged postoperative ventilation. Bashour and colleagues [11] also found that in patients aged 80 or more undergoing cardiac surgery, preoperative pulmonary disease was associated with an increased operative mortality, while Durand et al. [6] found preoperative pulmonary function Table 5 Factors predictive of increased long-term mortality in cardiac surgical patients who require prolonged mechanical ventilation Factor

10. Sternal resuture – operative re-approximation following dehiscence of initial closure (not elective closure after mediastinum electively ‘left open’). Of significance on multiple logistic regression six CARDIOVASCULAR SURGERY

⬍ ⬍ ⬍ ⬍ ⬍ ⬍

factors remained and these are listed with their P values in Table 4. Four different factors were identified that were predictive of increased long-term mortality in cardiac surgical patients. These are listed with their P values in Table 5 and are further defined below:

Table 2 Factors predicting requirement for prolonged mechanical ventilation after cardiac surgery Factor

P

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Impaired preoperative ejection fraction Increasing age Absence of preoperative aspirin Impaired preoperative pulmonary function tests

Cox regression Univariate (P) ⬍ 0.05 ⬍ 0.001 ⬍ 0.01 ⬍ 0.01

Multivariate (P) n.s. ⬍ 0.01 ⬍ 0.05 ⬍ 0.01

n.s., not significant.

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tests to be predictive in determining the need for prolonged ventilatory support. Bypass time has not previously been found to be associated with prolonged mechanical ventilation, but it has been associated with occurrence of perioperative infarction in unstable angina patients [12], a factor which, if severe, may necessitate prolonged ventilation caused by concomitant mechanical support. Determining survival following prolonged mechanical ventilation showed a 64% in-hospital survival rate. Kollef et al. [5] achieved an in-hospital survival rate of 80.4% in their prolonged ventilation group. However, their prolonged ventilation was defined as ⭓ 48 h whereas the present study concerns itself with a more extreme group and does not include patients at days 2–6 postoperatively – a factor which may contribute to the difference. Long-term survival of 58% in the present study remains unsupported, as no other studies have carried out long-term followup on this patient group. The factors predictive of increased intensive care mortality (Tables 3 and 4) include pre- and postoperative factors. Of particular significance is inotrope days (P ⬍ 0.001). This was found to be a significant predictor of increased intensive care mortality in a study in the long-stay population group [3], including patients who were still in the ICU at day 7 or more, but not necessarily ventilated. Sepsis (P ⬍ 0.001) was also a predictor of increased intensive care mortality. This was not, however, confirmed to chest infection as this factor also analysed was not found to be statistically significant. Dias et al. [7] had found that nosocomal pneumonia was significantly increased in prolonged ventilation patients. Li and Wang [13] found in a study of infected cardiac surgical patients that the mean hospital stay was prolonged by 14 days; however, there is no indication as to whether it is linked with prolonged ventilation, but is described as being associated with increased ‘oxygen therapy’ in comparison with a control group. Perioperative cerebrovascular accident (P ⬍ 0.01) is associated with prolonged mechanical ventilation, a not unsurprising finding as many of these patients are unable adequately to protect their airways in the early stages of a neurological complication. Requirement for fresh frozen plasma transfusion (P ⬍ 0.01) and coagulopathy as determined by a clotting screen (P ⬍ 0.05) are also associated with increased ICU mortality in cardiac surgical patients. This is supported by evidence from Pifarre [14] who found that in elderly patients undergoing cardiac surgery postoperative transfusion of blood products was related to an increased early mortality. Urban residence defined from the admission address of the patient (P ⬍ 0.01) is associated with both an increased requirement for, and increased ICU mortality following, prolonged ventilation. 380

Although the increase in mobility in society is evident, the mean age of this population is 62 years and it is unlikely that many patients have moved from a rural to an urban area when approaching retirement. The effect of urban dwelling on carbonization of lungs is evident to many surgeons, but the association with increased postoperative mortality is otherwise unsupported. Requirement for postoperative infusion of noradrenaline (P ⬍ 0.05) is associated with increased ICU mortality in the prolonged-ventilation group. This is supported by requirement for other inotropes as discussed above, both being an indirect measure of on-going myocardial dysfunction. Intra-aortic balloon counterpulsation (P ⬍ 0.05) is also associated with increased ICU mortality in the prolonged-ventilation group. Findings by Dias et al. [7] indirectly support this as it was determined that low-output syndrome and perioperative myocardial infarction were both linked with increased mortality in the prolonged-ventilation group. An acute confusional state (P ⬍ 0.05) requiring intravenous sedation was also linked with an increased ICU mortality. However, since the majority of patients requiring ventilation will require sedation it is difficult to draw any valid conclusion from this. Requirement for sternal resuture (P ⬍ 0.05) is also associated with increased ICU mortality data supported by Bryan et al. [15]. The four factors predictive of increased long-term mortality in prolonged ventilation patients are different from those indicative of ICU mortality. An impaired preoperative ejection fraction (P ⬍ 0.05) of ⬍ 30% is associated with increased long-term mortality; this has been well established from studies on coronary artery bypass patients [16–19] and on aortic valve patients [20]. Increasing age over the range 24–79 years is also associated with increased long-term mortality (P ⬍ 0.01). Horneffer and colleagues [21] found that coronary artery bypass grafting surgery in patients aged over 70 was linked with prolonged ventilation postoperatively, but that long-term survival was no different from that in a younger age group. Salomon et al. [22] also found that coronary artery bypass grafting patients aged over 75 required prolonged ventilation, although they did not associate this with increased long-term mortality. Age alone, however, is known to be associated with increased long-term mortality [16, 22–24]. Cohen and Lambrinos [8] found age to be an important predictor of outcome, but suggested that other factors were of equal influence. Abscence of preoperative aspirin medication is associated with increased long-term survival (P ⬍ 0.01) which has also been found in the prolonged intensive care stay population [3]. Impaired preoperative pulmonary function tests CARDIOVASCULAR SURGERY

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are associated with a poorer long-term prognosis (P ⬍ 0.01). Bashour et al. [11] found that perioperative mortality was increased in elderly patients with pulmonary disease, while Durand and colleagues [6] found pulmonary function tests to be an effective predictor of the likelihood of developing postoperative complications and the need for prolonged ventilation support; however, no comment is made on long-term survival in these series. In conclusion, from the factors analysed, four were identified that predicted an increased requirement for prolonged ventilation, namely chronic obstructive airways disease, prolonged operation, bypass time, and urban residence. A further five factors were associated with increased intensive care mortality, namely inotrope days, sepsis, perioperative cerebrovascular accident, fresh frozen plasma requirement and urban residence. In addition, four other factors were linked with increased long-term mortality, namely impaired preoperative ejection fraction, increasing age impaired preoperative pulmonary function, and abscence of preoperative aspirin. It follows therefore that, in planning ventilation facilities and in the continuing management of cardiac surgical patients requiring prolonged ventilation, these 12 factors should be strongly considered.

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