Elsevier

The Lancet

Volume 378, Issue 9800, 15–21 October 2011, Pages 1379-1387
The Lancet

Articles
Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(11)61144-6Get rights and content

Summary

Background

For some surgical procedures to be done, a patient's blood circulation needs to be stopped. In such situations, the maintenance of blood flow to the brain is perceived beneficial even in the presence of deep hypothermia. We aimed to assess the benefits of the maintenance of antegrade cerebral perfusion (ACP) compared with deep hypothermic circulatory arrest (DHCA).

Methods

Patients aged 18–80 years undergoing pulmonary endarterectomy surgery in a UK centre (Papworth Hospital, Cambridge) were randomly assigned with a computer generated sequence to receive either DHCA for periods of up to 20 min at 20°C or ACP (1:1 ratio). The primary endpoint was change in cognitive function at 12 weeks after surgery, as assessed by the trail-making A and B tests, the Rey auditory verbal learning test, and the grooved pegboard test. Patients and assessors were masked to treatment allocation. Primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN84972261.

Findings

We enrolled 74 of 196 screened patients (35 to receive DHCA and 39 to receive ACP). Nine patients crossed over from ACP to DHCA to allow complete endarterectomy. At 12 weeks, the mean difference between the two groups in Z scores (the change in cognitive function score from baseline divided by the baseline SD) for the three main cognitive tests was 0·14 (95% CI −0·14 to 0·42; p=0·33) for the trail-making A and B tests, −0·06 (−0·38 to 0·25; p=0·69) for the Rey auditory verbal learning test, and 0·01 (−0·26 to 0·29; p=0·92) for the grooved pegboard test. All patients showed improvement in cognitive function at 12 weeks. We recorded no significant difference in adverse events between the two groups. At 12 weeks, two patients had died (one in each group).

Interpretation

Cognitive function is not impaired by either ACP or DHCA. We recommend circulatory arrest as the optimum modality for patients undergoing pulmonary endarterectomy surgery.

Funding

J P Moulton Charitable Foundation.

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) was first described in the UK in 1951.1 It is now more widely recognised and develops in up to 3·8% of patients after acute pulmonary embolism.2 CTEPH leads to functional impairment and confers a poor prognosis,3 but many patients can be cured by pulmonary endarterectomy (PEA), having substantial improvement in symptoms and survival.4, 5, 6

For PEA to be successful, a complete surgical endarterectomy should be done, which requires a bloodless operative field to allow for precise dissection and maximum clearance of obstructive material. The most widely used technique is deep hypothermic circulatory arrest (DHCA), which allows complete cessation of blood flow and therefore optimum operating conditions. PEA surgery with DHCA leads to a reproducible reduction in pulmonary artery pressure and low in-hospital mortality.7 Because periods of DHCA are usually limited to 20 min, permanent neurological injury is rare, although complications have been reported.8 Detailed assessment of the effect of PEA with DHCA on cognitive function has not been reported.

Some surgical groups have suggested that PEA is possible with a lesser degree of hypothermia (>28°C) and reduced periods of DHCA9, 10 or partial circulatory arrest with continuous antegrade cerebral perfusion (ACP) to the brain.11 None of these alternative techniques that aim to decrease the potential morbidity from DHCA have been assessed in a randomised manner. These techniques have received criticism because of the potential risk of incomplete endarterectomy and a less successful operation.9 A fundamental compromise exists between the provision of sufficient operating time with a clear field to allow a complete endarterectomy and minimisation of the period that a patient's brain is not perfused. Other surgical procedures, mainly on the aorta, need cessation of blood circulation and use the same techniques to protect the brain while enabling surgery.

This prospective, randomised blinded study was done to compare cognitive and clinical outcomes in a homogeneous cohort of adult patients with CTEPH undergoing PEA surgery randomly allocated to either DHCA or ACP.

Section snippets

Study population

All patients aged 18–80 years who were referred to the UK national centre for PEA surgery (Papworth Hospital, Cambridge) between December, 2006, and March, 2009, were eligible to be included in the study. The institution had equal experience with both methods of cerebral management for PEA surgery when the trial started.

Patients were excluded if they could not complete cognitive functions tests (eg, sight or hearing impairments, physical barriers such as severe arthritis), were not fluent in

Results

74 of 196 screened patients were randomly allocated to one of the two treatment groups (figure 1). Overall in-hospital mortality for the whole cohort was 1·4% (1 of 74 patients) and survival at 1 year was 96% (71 of 74 patients). Characteristics of patients at baseline were much the same between the two groups (table 1).

We recorded no difference in cognitive outcome between treatment groups (Figure 2, Figure 3). For the primary outcome at 12 weeks, the mean differences between the Z scores were

Discussion

Our findings show no benefit in the maintenance of brain perfusion over temporary periods of DHCA of up to 20 min at 20°C (total cumulative time 36 min) in patients undergoing PEA. Our study shows that although perfusion of the brain might be safe, no evidence exists that it is better than DHCA, because we did not detect any difference between the groups in cognitive function measurements. Perfusion of the brain is a laudable goal, but should not detract from the importance of surgical success.

References (28)

  • G Piazza et al.

    Chronic thromboembolic pulmonary hypertension

    N Engl J Med

    (2011)
  • R Condliffe et al.

    Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension

    Am J Respir Crit Care Med

    (2008)
  • DH Freed et al.

    Survival after pulmonary thromboendarterectomy: effect of residual pulmonary hypertension

    J Thorac Cardiovasc Surg

    (2010)
  • SW Jamieson et al.

    Pulmonary endarterectomy: experience and lessons learned in 1,500 cases

    Ann Thorac Surg

    (2003)
  • Cited by (132)

    • Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT

      2021, Journal of Heart and Lung Transplantation
      Citation Excerpt :

      PEA using deep hypothermic circulatory arrest is the standard-of-care for CTEPH. The technique has been adopted by the vast majority of the surgical centers performing PEA and progressively refined with increasing experience.85,173-178 Currently, patients with disease located in the segmental and subsegmental pulmonary artery on imaging are candidates for PEA with excellent early and long-term outcome in expert centers.85,178

    View all citing articles on Scopus

    Authors contributed equally

    View full text