Day or Night—Does the Time of Liver Transplantation Matter?

James Neuberger


Abstract and Introduction


Surgical complications are a major cause of avoidable medical mistakes, and might occur more frequently when surgery is performed at night. In a recent study, Lonze et al. found that patients who underwent liver transplantation surgery at night had a longer operative time and a greater risk of early death than those who underwent surgery during the day.


Over the past decade, a drive to reduce the number of surgical interventions carried out at night has been initiated, as well as a drive to reduce the working hours of clinicians (especially those in training). These initiatives have led the surgical teams at The Johns Hopkins University, Baltimore, MD, USA, and Albert Einstein Medical Center, Philadelphia, PA, USA, to conduct a retrospective analysis of the outcomes and incidence of complications following liver transplantation and correlate these with the time of surgery.[1] Data were collected from 578 liver transplantations carried out between 1995 and 2008. The start of surgery was considered either in two 12 h periods; day (3.00 am to 3.00 pm) and night (3.00 pm to 3.00 am), or in eight 3 h periods. The 6.00–9.00 am slot was considered as the reference group when analyzing outcomes using the 3 h intervals. Complications were classified in four categories: wound (including infection, hematoma, incisional hernia and dehiscence); vascular (including hepatic artery thrombosis or aneurysm, hepatic or portal venous thrombosis); biliary (including bile leak, bile duct stenosis and biliary sludge); and other (including peritonitis and enteric fistula). Except for incisional hernias, only those complications that occurred within 30 days of surgery were considered in the analysis.

When only those risks that reached statistical significance were analyzed, operations with a start time between 3.00 pm and 6.00 pm had the greatest risk of complications overall (odds ratio [OR] 2.2). This finding is mainly the result of an increase in vascular complications, which were most common in surgeries with a start time between 3.00 pm and 6.00 pm. By contrast, wound complications were most common when surgery started between 6.00 pm and 9.00 pm (OR 2.9). Operative time was longest in those surgeries that were started between midnight and 3.00 am. When night-time and daytime starts were compared, patients who underwent surgery at night had a longer operative time and a greater risk of early death than those who underwent surgery during the day.

Of course, there are limitations to this analysis, many of which the authors acknowledge. The analysis is retrospective, with all the associated inherent concerns. Furthermore, the number of surgeries analyzed is quite small and the recruitment covered a long period of time during which many changes in practice probably occurred. Lonze et al.'s selection and grouping of complications could be criticized: furthermore, some or all of the complications might be caused by one or more of several factors including, of course, the possibility that the complications might be associated with surgical or anesthetic skills being less acute at night. More importantly, the start time of surgery is not random. Indeed, surgeons might decide to operate at night to reduce the cold ischemia time, especially when the donor or graft is of high risk. However, even with all the inherent pitfalls and caveats, the study by Lonze and colleagues does raise an important question: can liver transplantation be done safely at night or should the start be deferred until the morning?

Intuition and common sense suggest that major surgery, like any other activity that demands concentration, manual dexterity, physical stamina and teamwork, should start in the morning when all those involved in the care of the patient are alert and when all routine support services are in place. However, as is often the case, a simplistic view might not be the correct one. The evidence that suggests outcomes are worse when surgery is done at night as a consequence of night-time working is far from overwhelming.[2–6] In addition, the effects of night-time operating and sleep deprivation are frequently confused. Transplant surgeons rarely have an uninterrupted night's sleep before the transplant; they are often disturbed by interruptions from coordinators and others asking about the donor or recipient and might have spent some time discussing the risks with the potential candidate. Thus, a morning start might follow a poor night's sleep.

Postponing surgery, even by a few hours, could result in added risks for the recipient: prolonged cold ischemia times will lead to an increased risk of primary nonfunction or delayed function (especially in a steatotic graft). In addition, prolonged cold ischemia times are associated with an increased risk of biliary complications and possibly more aggressive consequences of HCV graft infection.[7,8] For the few patients with fulminant hepatic failure, a delay in transplantation might result in the development of irreversible complications, such as cardiovascular instability or irreversible cerebral edema and brainstem coning, that render the procedure futile.

Even if the arguments for delaying surgery to enable a morning start are accepted, what are the logistics of managing the donation process to achieve this without prolonging cold ischemia time? Consent for donation is generally obtained in the late morning or early afternoon, according to preliminary and unaudited data provided by the UK National Transplant Registry on the timings of the donation pathway of 100 liver transplants across the seven designated transplant centers in the UK from January 2010 (UK National Transplant Registry, unpublished data) (Figure 1). The interval from consent both to the start of the retrieval process and to the start of the transplant surgery is variable. However, for donations after brain death (DBD), the intervals are shorter the later in the day the consent is taken, whereas for donations after cardiac death (DCD), the converse is true.

Figure 1.

The relationship between the time when consent is obtained and the start of retrieval and between consent time and the start of transplant. a | Donations after brain death and b | donations after cardiac death. Data from the UK National Transplant Registry.

The interval between obtaining consent and the start of the retrieval is affected by many factors. In my experience, the timing is dependent on ensuring the family of the donor are properly cared for, as well as logistic issues such as finding an available anesthetist, theater staff and theater time. The time to the start of the transplant will depend on various factors, including the time taken to select and contact the recipient, the time taken for the recipient to reach the hospital, be assessed and prepared for surgery, as well as the time required to transport the graft to the patient. Although numbers are smaller for DCD than for DBD and do not reach statistical significance, data from the UK National Transplant Registry raise the possibility that where consent is taken in the afternoon, the transplant is more likely to take place at night. Grafts from DCD are also associated with a greater risk of complications than those from DBD and so an increased cold ischemic time might further increase the risk for the recipient. Delaying retrieval to enable a morning start with a short cold ischemic time is sometimes possible. However, this delay would put more pressure on grieving families and personal and anecdotal experience suggests that sometimes delay in retrieval can result in withdrawal of consent. The critical cold ischemic time, after which the risk of complications starts to increase considerably, varies between organs: so the practice for liver transplants will probably differ from bowel, kidney, heart, lung or pancreas transplant practice.

Overall, the effect of the timing of surgery might be important and the study by Lonze et al.[1] should be repeated. On the present evidence, there is little need to ensure that the start time of surgery is postponed to enable a morning start. Instead, timings should be determined by the needs to care for the donor families, minimize cold ischemic times and ensure that the recipient is well prepared and assessed and full support is available.