Do patients who require re-exploration for bleeding have inferior outcomes following cardiac surgery?

Abstract

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Do patients who require return to theatre (RTT) for bleeding have inferior outcomes following cardiac surgery? Altogether, 598 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In summary, patients who bleed following cardiac surgery and then RTT have increased mortality and experience greater morbidity, including neurological, respiratory and renal complications, which result in increased length of intensive care unit stay and hospital stay. It is not easy to dissect the relative contribution of the blood loss and consequent haemodynamic instability, the RTT and the increased blood product consumption to the inferior outcomes observed, as there is evidence that each is important. However, several studies have demonstrated RTT to be an independent predictor of morbidity and mortality, even when controlling for amount of transfusion. Patients who bleed and RTT beyond 12 h postoperatively appear to have the poorest outcomes, suggesting that the decision to RTT should not be delayed if there are concerns over significant bleeding, to ensure the best patient outcomes.

INTRODUCTION

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

Do [patients undergoing cardiac surgery] who [require return to theatre for bleeding] have inferior [clinical outcomes]?

CLINICAL SCENARIO

A 75-year-old man is in the cardiac recovery area after undergoing coronary artery bypass grafting. There is a concern that he may be bleeding due to high-drain output over the first 3 h postoperatively. You decide to re-explore the patient and find a bleeding side branch on a vein graft. You are considering implementation of an initiative to reduce the incidence of mediastinal bleeding and return to theatre rate in your centre and want to understand the potential clinical impact. You resolve to search the literature to find the best evidence.

SEARCH STRATEGY

A systematic search was performed on the MEDLINE database from 1950 to June 2018 using the OVID interface with the terms [cardiac surgery OR valve surgery OR coronary artery bypass] AND [re-exploration OR reoperation OR return to theatre] AND [bleeding OR tamponade].

SEARCH OUTCOME

Five hundred and ninety-eight papers were found using the reported search. From these, 8 papers were identified that provided the best evidence to answer the question. These are presented in Table 1.

RESULTS

A meta-analysis was published by Biancari et al. [2] in 2011 which summarized outcomes from 8 studies examining the impact of return to theatre (RTT). Re-exploration was associated with significantly poorer outcomes. For 30-day mortality, the risk ratio (RR) was 3.27. Postoperative morbidity was also increased (stroke RR = 3.27; acute renal impairment RR = 3.70; prolonged mechanical ventilation RR = 3.39 and sternal wound infection RR = 4.52). Mortality was increased in patients requiring greater blood transfusion, in both the RTT and control groups. Patients returning to theatre >12 h postoperatively had poorer survival (RR = 5.22, P < 0.0001). The authors concluded that re-exploration for bleeding carries a significantly increased risk of postoperative mortality and morbidity.

Since the publication of the meta-analysis, the remaining 7 studies have been published, with 5 studies using propensity matching. The first of the propensity-matched studies was reported by Vivacqua et al. [3] in 2011 from the USA. They observed an RTT incidence of 3.0% describing outcomes of 566 patients over a 10-year period. Patients RTT had increased 30-day mortality (8.5% vs 1.8%, P < 0.0001) and experienced increased morbidity. They had a greater incidence of prolonged ventilation (42% vs 12%, P < 0.0001), renal failure (6.7% vs 1.9%, P < 0.0001) and length of hospital stay >14 days (26% vs 12%, P < 0.0001). Outcome was the worst in patients who returned to the theatre and also required significant blood transfusion. However, mortality and morbidity were higher in patients RTT even ‘after’ adjusting for the amount of blood transfusion and in patients receiving significant blood transfusion but not RTT. The authors conclude that both re-exploration and higher transfusion requirements independently contribute to increased morbidity and mortality.

In 2012, Kristensen et al. [4] propensity matched 101 patients RTT at a centre in Denmark. They reported an incidence of 7.0% over the 3-year period of study. The authors observed increased 30-day mortality for patients RTT (15.8% vs 5.7%, P < 0.001) but did not demonstrate any differences in major morbidity—although restricted their evaluation to stroke, sternal infection and myocardial infarction. They did, however, note a significantly increased peak creatinine in patients RTT (160.4 vs 126.1, P < 0.001). The authors also reported that earlier RTT was associated with improved outcome, observing that for patients RTT, those who survived were re-explored earlier (561 min vs 406 min, P = 0.06). The authors concluded that re-explored patients had a greater increase in postoperative creatinine and higher mortality. This study did not report on postoperative blood product consumption.

In 2015, Haneya et al. [5] in Germany matched 209 patients (an incidence of 2.6% over the 6-year period of study). Inferior outcomes were observed for patients RTT. The 30-day mortality was 9.6% vs 3.3% (P = 0.02). Major morbidity was also greater: renal failure (P = 0.01), sternal wound infection (P < 0.01), pulmonary infection (P < 0.01), prolonged ventilation (P < 0.01) and inotropic support (P < 0.01). This resulted in a prolonged intensive care unit (ICU) stay (5 days vs 2 days, P < 0.01) and hospital stay (11 days vs 9 days, P < 0.01). Interestingly, on multivariate analysis, RTT was not an independent predictor of 30-day mortality, but blood transfusion was. Similar to other studies, there was inferior survival if patients were re-explored >12 h postoperatively (P = 0.003). The authors conclude that re-exploration is associated with increased mortality and morbidity, as well as increased blood product consumption.

Ohmes et al. [6] compared outcomes for 189 propensity-matched patients RTT (an incidence of 2.6% over the 8-year period of study). There was greater in-hospital mortality (6.7% vs 3.4%, P = 0.05) and an increased incidence of major adverse events (31.8% vs 11.2%, P < 0.01), prolonged ventilation (24.6% vs 8.4%, P < 0.001) and gastrointestinal complications (5.6% vs 1.7%, P = 0.046). There was no significant difference in the incidence of stroke, deep sternal wound infection, sepsis or renal failure. RTT >560 min postoperatively was associated with increased morbidity in keeping with other reports, which the authors attribute to greater blood drainage. The authors concluded that RTT significantly increases in-hospital mortality and morbidity after cardiac surgery. This study did not report on postoperative blood product consumption.

In 2017, Tambe et al. [7] reported the only study which failed to demonstrate poorer outcomes for patients RTT. They matched 779 patients from 3 centres in Denmark over the 7-year period of study, with an overall RTT incidence of 5.7%. The authors describe protocol-driven RTT with drainage >200 ml/h for 2 consecutive hours as a trigger. The authors imposed strict propensity matching criteria and excluded 94 RTT patients. They demonstrated no difference in 30-day mortality [odds ratio (OR) 1.08], 6-month mortality (OR 0.75), sternal wound infection (OR 0.86), acute renal failure (OR 0.59), stroke (OR 0.59) or myocardial infarction (OR 0.73). The authors included the number of red blood cell units transfused in their propensity criteria, and as a result, the control group had high RBC consumption and, therefore, mediastinal blood loss. It is noteworthy that when they compared outcomes of the 873 patients RTT to the 15 350 who did not, there was a significant increase in 30-day mortality in the RTT group (8.59% vs 2.56%, P < 0.0001). The authors concluded that re-exploration is not associated with a higher frequency of severe postoperative complications, which is likely due to the difficulty in distinguishing between the contribution of RTT and blood transfusion to morbidity and mortality.

The final 2 studies were unmatched cohort studies. The first was reported by Fröjd and Jeppsson [8] in 2016 from Sweden. They compared 320 patients RTT to 5055 patients who did not. The incidence of RTT was 6.3% over the 4-year period of study. There was higher 30-day (7.6% vs 2.4%, P < 0.0001) and 90-day (11.7% vs 3.4%, P < 0.0001) mortality in patients RTT. Additionally, there was significant morbidity: prolonged ICU stay (OR 3.57, P < 0.0001), prolonged period of ventilation (OR 3.64, P < 0.0001), increased incidence of mechanical support (OR 1.99, P = 0.014) and increased incidence of renal failure (OR 2.36, P < 0.0001). Patients RTT required greater blood product transfusion although the authors did not differentiate RBC and coagulation products or analyse this further. RTT was an independent predictor of increased mortality in multivariate analysis. The authors concluded that excessive bleeding leading to re-exploration is associated with increased early postoperative mortality rate and increased morbidity.

Finally, Ruel et al. [9] reported 661 patients RTT versus 16 132 controls from Canada. The RTT incidence during the 12-year period of study was 3.9%. In-hospital mortality was greater for patients RTT (12% vs 2.8%, P < 0.001). There was also increased morbidity, prolonged ICU stay (3 days vs 1 day, P < 0.001), prolonged hospital stay (12 days vs 7 days, P < 0.001) and a higher incidence of atrial fibrillation (OR 1.5, P = 0.006), renal failure (OR 17.9, P < 0.001) and wound infection (OR 2.0, P = 0.001). They reported a significant impact of RTT >12 h postoperatively on in-hospital mortality (OR 6.4, P < 0.001). The authors also noted that the number of intraoperative RBC units transfused was associated with mortality and that this was additive to the impact of RTT. The authors concluded that re-exploration is associated with increased hospital mortality and morbidity. This study did not report on postoperative blood product consumption.

CLINICAL BOTTOM LINE

Patients who bleed following cardiac surgery and then RTT have increased mortality and experience greater morbidity, including neurological, respiratory and renal complications which result in increased length of ICU stay and hospital stay. It is not easy to dissect the relative contribution of the blood loss and consequent haemodynamic instability, the RTT and the increased blood product consumption to the inferior outcomes observed, as there is evidence that each is important. However, several studies have demonstrated RTT to be an independent predictor of morbidity and mortality, even when controlling for amount of transfusion. Patients who bleed and RTT beyond 12 h postoperatively seem to have the poorest outcomes, suggesting that the decision to RTT should not be delayed if there are concerns over significant bleeding to ensure the best patient outcomes.

Conflict of interest: none declared.

REFERENCES

Author notes