Bloodless Intensive Care: A Case Series and Review of Jehovah's Witnesses in ICU
(Anaesthesia and Intensive Care)SUMMARY The objective of this study was to assess the outcome of Jehovah's Witness (JW) patients admitted to a major Australasian ICU and to review the literature regarding the management of critically ill Jehovah's Witness patients. All Jehovah's Witness patients admitted to the ICU between January 1999 and September 2003 were identified from a prospective database. Their ICU mortality, APACHE II scores, APACHE II risk of death and ICU length of stay were compared to the general ICU population. Twenty-one (0.24%) out of 8869 patients (excluding re- admissions) admitted to the ICU over this period were Jehovah's Witness patients. Their mean APACHE II score was 14.1 (7.0), the mean APACHE II risk of death was 21.2% (16.6), and the mean nadir haemoglobin (Hb) was 80.2 g/l (36.4). Four out of 21 Jehovah's Witness patients died in ICU compared to 782 out of 8848 non- Jehovah's Witness patients (19.0% vs 8.8%, P=0.10, chis quare). The median ICU length of stay in both groups was two days (P=0.64, Wilcoxon rank sum). The lowest Hb recorded in a survivor was 23 g/ l. Jehovah's Witness patients appear to be an uncommon patient population in a major Australasian ICU but are not over-represented when compared with their prevalence in the community. Despite similar severity of illness scores and predicted mortality to those in the general ICU population, there was a trend towards higher mortality in Jehovah's Witness patients. Key Words: JEHOVAH'S WITNESS: bloodless medicine; bloodless surgery; intensive care; anaemia; hyperbaric oxygen; erythropoietin For it seemed good to the Holy Ghost, and to us, to lay upon you no greater burden than these necessary things; That ye abstain ... from blood ... from which if ye keep yourselves, ye shall do well.1 This quotation formed part of a letter from the Apostles to the Gentiles in Antioch and provided the basis for one of the tenets of Charles Taze Russsell, who founded the Jehovah's Witness (JW) movement in the United States in the late nineteenth century. The estimated six million currently practising Jehovah's Witnesses believe that the Bible is literally the word of God and eschew the therapeutic use of blood and its components. Specifically, they will not accept whole blood, red blood cells, platelets, fresh frozen plasma or cryoprecipitate. The use of vaccines, organ transplantation, albumin or immunoglobulins are designated "matters of conscience" and the individual can decide whether or not to accept these therapies2. Receiving their own blood is generally acceptable only when it passes through a closed circuit in continuity with the patient, such as cardiopulmonary bypass or haemodialysis3. However, there is dissension amongst individual Jehovah's Witnesses regarding these prohibitions and some will accept blood products under certain circumstances4. The literature concerning the management of JW patients in the intensive care unit (ICU) is limited. The objective of this study was to assess the outcomes of JW patients in ICU and to review the literature regarding the management of critically ill JW patients. Based on evidence that anaemic postoperative patients who refuse blood transfusions have a greater mortality than patients willing to accept blood transfusion5, it was hypothesised that JW patients might have both a greater ICU length of stay and higher mortality than that of other ICU patients. MATERIALS AND METHODS The Alfred Hospital provides the State of Victoria, Australia, with quaternary services for trauma, burns, hyperbaric medicine, and heart and lung transplantation, in addition to other tertiary care typical of a level III ICU. All JW patients admitted to the ICU between January 1999 and September 2003 were identified from a prospective database which specifically codes for Jehovah's Witnesses. A retrospective case series was established. The APACHE II scores, APACHE II risk of death, ICU length of stay and ICU mortality of these JW patients were compared to the non-JW population over the same period. Data on the patients were collected prospectively from the medical charts by trained data-collectors, except nadir haemoglobin concentrations and erythropoietin use in the JW patients, which was gathered retrospectively by the authors. Following WHO guidelines, anaemia was defined as a haemoglobin (Hb) of less than 130 g/l in men and less than 120 g/l in women. RESULTS The JW patients are presented in Table 1. Twenty-one JW patients (0.24%) out of a total of 8869 patients (excluding re-admissions) were admitted to ICU between January 1999 and September 2003. The mean age of the JW patients was 57.8 years (18.9) and the mean nadir haemoglobin concentration was 80.2 g/l (36.3). Twenty of the patients (95.2%) had anaemia, with the lowest recorded Hb in a survivor being 23 g/l. The mean APACHE II score was 14.1 (7.0) and the median ICU length of stay was 2 days (interquartile range 1-5). They were a heterogeneous group of patients, with the majority (12 out of 21 (57.1%)) being admitted to ICU for postoperative care. The results comparing JW and non-JW patients are presented in Table 2. There were no statistically significant differences in APACHE II scores (14.1 vs 15.1, P=0.43, Wilcoxon rank sum), APACHE II risk of death (21.2% vs 20.9%, P=0.47, one-tailed t-test for independent samples (equality of variances was not tested; the P value was the same assuming either equal or unequal variance)) or ICU length of stay (median 2 days for both groups, P=0.64, Wilcoxon rank sum) between JW and non-JW patients. Four of the 21 JW patients died and 782 of the 8848 non-JW patients died (19.0% vs 8.8%, P=0.10, chi square). Only one of the four JW patients died solely of anaemia (patient 15). Two others died with extremely low haemoglobin concentrations that contributed to their morbidity: patient 20 died seven days after suffering a respiratory arrest on a background of severe left ventricular failure and inoperable aortic valve disease; and patient 9 died of multiorgan failure following urgent coronary bypass grafting. Patient 19 had significant pre-existing co- morbidities and died from community-acquired pneumonia. He did not have severe anaemia. None of the JW patients discharged from ICU subsequently died in hospital. DISCUSSION JW patients are an uncommon patient population in ICU. The largest published series of anaemic JW patients, with three hundred patients, involved twelve centres in the U.S.A. over a thirteen- year period5. It studied all hospitalized postoperative JW patients (excluding cardiac surgical patients) with a serum Hb of less than 80 g/l, irrespective of whether they were in ICU. By comparison, our series was a single centre cohort over a four-year, nine-month period and looked specifically at JW patients in ICU regardless of Hb level. Only 0.24% of the total ICU admissions in this period were JW patients. The 2001 Census of Population and Housing by the Australian Bureau of Statistics showed that there were approximately 81,100 JWs in Australia at this time, or 0.4% of the population. Thus, JW patients do not appear to be over-represented in ICU. The small size of the cohort limits our ability to draw definitive conclusions about this patient population. Nonetheless, despite similar APACHE II scores, APACHE II risk of death and ICU length of stay, the JW patients exhibited a trend to higher mortality compared with that of the non-JW patients. Carson and co- workers5 obtained similar conclusions, demonstrating increasing mortality with decreasing Hb concentration, with mortality rising sharply in patients with a Hb of less than 50 to 60 g/l. In our series, two out of five patients (40%) died with a nadir Hb of less than 50 g/l, compared with two out of sixteen patients (12.5%) with a Hb of greater than 50 g/l. Importantly, neither series had a patient who survived a Hb of less than 20 g/l. Eleven patients (52.3%) in our series did not receive recombinant human erythropoietin (rHuEpo). Some of these patients refused to have rHuEpo administered to them after risks and benefits were discussed. However, at this time in the ICU there was no prospective protocol for managing JW patients or for using rHuEpo and management decisions were at the discretion of the treating ICU specialist. The trend we have observed towards higher mortality in JW patients in ICU has implications for their management. There follows a literature review on the management of JW patients in ICU, addressing general treatment issues, how to compensate for anaemia without transfusion, strategies for perioperative management and organization of health care provision. TABLE 1 JW patients TABLE 2 Results comparing JW patients and non-JW patients A REVIEW OF THE MANAGEMENT OF JW PATIENTS IN ICU General ICU Management Managing JW patients in ICU is challenging. Optimizing the patient's oxygen delivery can be difficult, as inadequate fluid resuscitation will compromise cardiac output, whereas liberal fluid resuscitation can cause haemodilution and further falls in haemoglobin level. There are ethical and medicolegal issues concerning withholding life-saving treatment on patients unable to communicate their wishes clearly. The law in Australia regarding advanced directives is ambiguous and there have been calls for clarification of the rights of patients who refuse blood transfusions6. New therapies havebeen developed which have yet to be fully evaluated in JW patients, such as recombinant factor VII7. The literature abounds in anecdotal reports of JW patients undergoing complex surgery or surviving profound anaemia in ICU8-11. Patient survival is often attributed to new methods of treatment, although the evidence for this is limited12,13. However, there is evidence to support a number of treatment modalities and some general recommendations can be made regarding the management of JW patients in ICU. - As noted in the introduction, there is some variation in the blood products that JW patients will accept. Where possible, a direct and confidential discussion should be conducted with the patient and thoroughly documented14. - Referral of the patient to a different institution that has greater expertise and experience with JW patients may be appropriate3. Whilst there are several dozen centres in the U.S.A. that promote bloodless medicine and surgery, there is only one in Australia (Kayeela Hospital, East Fremantle, Western Australia) and it does not have an ICU. A regional tertiary centre may suffice if specialized referral centres are unavailable. - Rationalizing the frequency and volume of blood sampling is important to minimize blood loss. Two epidemiological studies of ICU patients have demonstrated similar figures for the mean volume of blood taken for testing from critically ill patients: 42.5 ml/day in one study15 and 41.1 ml/day in the other16. The more unwell the patient, the more blood that is likely to be taken. The use of minimum-volume sampling tubes should be universal in JW patients. Monitoring equipment that minimizes blood sampling, such as oximetric pulmonary artery catheters or continuous intra-arterial blood gas analysers, should be utilized if available. - A multidisciplinary approach should be employed for any complex problems in these patients, involving all relevant specialists including a haematologist. A plan should be drawn up in advance to deal with any foreseeable complications17. - Only senior personnel should perform procedures that carry a risk of significant blood loss. - Minimizing oxygen requirements, with sedation, ventilation and maintenance of euthermia, may be of benefit in patients with severe anaemia9. - Critically evaluating the need for anti-coagulant or anti- platelet therapy is important, as these may contribute to or precipitate life-threatening haemorrhage17. Compensating for Anaemia Erythropoietin One regimen of recombinant human erythropoietin (rHuEpo; 40000 U once per week subcutaneously) has been shown to reduce transfusion requirements and increase haemoglobin in the critically ill18. However, the long-term effects of this approach are unknown and its utility in general ICU patients has been questioned19. It has not been adequately studied in JW patients. A trial involving forty post- operative JW patients demonstrated a faster rise in haemoglobin levels with a different regimen of rHuEpo (300 U/kg intravenously three times a week for one week, then 150 U/kg three times a week thereafter) than with placebo20. The use of rHuEpo in anaemic JW patients is regarded by many as standard treatment8. On the basis of existing evidence, all JW patients in the ICU should receive rHuEpo if they are anaemic or at risk of major blood loss. Therapy with rHuEpo takes at least five days before a demonstrable rise in haemoglobin is evident3. Adequate stores of vitamin B12, folate and iron are essential for it to be effective. Oral iron supplementation is regarded as standard therapy14. There is little evidence contradicting this but at least one study shows benefits from intravenous iron administration in a preoperative population21 and another in a dialysis population22. Consequently, some authorities recommend administering intravenous iron once every one to two weeks17. Corwin and co-workers used an oral iron preparation for all patients, changing to intravenous iron administration only if there was an inadequate response on the basis of iron studies (defined as a transferrin saturation <20% or a decrease in serum ferritin <225 pmol/l)18. Hyperbaric Oxygen Whilst there is a sound physiological rationale to support the use of pulsed hyperbaric oxygen (HBO) in patients with severe anaemia to alleviate oxygen debt9, there is very little clinical evidence demonstrating a clear improvement in outcome. Treating critically ill patients with severe anaemia and consequent multiorgan failure is a challenge for any hyperbaric facility and HBO is not a practical option for many patients. However, severe anaemia is accepted as an indication for HBO by a number of expert committees23 and it should be considered for JW patients with inadequate oxygen delivery in whom other therapies have failed. Artificial Oxygen Carriers Artificial oxygen carriers are classified into two groups: haemoglobin-based oxygen carriers (HbOC) and perfluorocarbons (PFC). HbOCs are currently undergoing phase III trials in the U.S.A. These products obtain their haemoglobin base from one of three sources: bovine blood, outdated units of human red blood cells or from recombinant technology. Many JW patients will not accept these products, especially from human or bovine sources. Recombinant HbOCs are in development, but immune reactions to the liposomal membrane in which the haemoglobin molecule is encapsulated have proven to be problematic in animal models25. PFCs are inert compounds with low surface tension and a huge capacity for dissolving gases. They are regarded as experimental in humans and problems with them include the need for the patient to be kept on high levels of supplemental oxygen, the induction of a flu- like illness, and platelet sequestration26. At present, no artificial oxygen carriers are approved for human use anywhere outside South Africa17, many of them will not be acceptable to JW patients should their source become apparent, and none are easily obtainable in Australia. Peri-operative Management Preoperative Consultation This is an important discussion, allowing the patient and clinician to establish what blood products, surgical and anaesthetic techniques are acceptable. Some centres have a protocol guiding this discussion, at which an anaesthetist and a haematologist are present14. When relevant, providing ICU staff with a transcript of the preoperative discussion or involving the ICU specialist directly would be valuable in planning and guiding the postoperative care of the patient. Preoperative Erthropoietin Many studies have demonstrated the safety and efficacy of using preoperative rHuEpo starting three to four weeks prior to surgery, although it is an expensive strategy14. Preoperative Autologous Blood Donation This is not acceptable to JW patients, as the blood is not kept in continuity with the patient17. Acute-normovolaemic Haemodilution This well-described technique involves removing blood from the patient at the beginning of the operation and replacing it with crystalloid or colloid. The blood can then be re-infused near the end of the procedure leading to a relative conservation of red blood cells and clotting factors, as any blood lost intra-operatively will be diluted. This is acceptable to JW patients as long as the blood is kept in continuity with the patient3. Blood salvage "Cell saver" devices are generally acceptable intra-operatively, as the blood is perceived to remain in contact with the body. Postoperative salvage, however, such as collection of blood from intercostal or mediastinal drains and re-infusion back into the patient, is generally not acceptable14. Systemic anti-fibrinolytics Aprotinin, aminocaproic acid and transexamic acid have all been used in the perioperative period to decrease bleeding, or in circumstances such as trauma or gastrointestinal haemorrhage. There is considerable evidence to support their use, with demonstrable reductions in blood loss27 and mortality28. The choice of agent will be dependent on drug availability, patient characteristics and the nature of the surgery. Controversy remains as to which of these is the best agent at reducing bleeding in specific circumstances29-31. Surgical technique Electrocautery and devices such as the Cavitational Ultrasonic Surgical Aspirator (CUSA; Valleylabs, Boulder, Colorado, U.S.A.) and the Harmonic Scalpel (Ethicon, Cincinnati, Ohio, U.S.A.) have considerably improved the surgeon's ability to rapidly achieve haemostasis17. Their efficacy obviously depends upon the surgery and the experience of the operator. Organization As intensive care specialists become more aware of the immunomodulating effects of blood transfusion and their potentially deleterious consequences32-34 and as evidence accumulates overturning the traditional indications for red blood cell transfusions in the critically ill35, it is conceivable that some of the strategies applied at present to JW patients in order to obviate the need for transfusion may be utilized in a wider population of critically ill patients. Bloodless medicine and surgery programs are springing up worldwide as the need for such practices increases. Co- ordination of intensive care specialists, haematologists, anaesthetists, surgeons and administrative personnel is essential in order to facilitate the smooth running of these programs12. There is a need for individual institutions to establish protocols to guide the management of patients who refuse allogeneic blood transfusions. Fundamentally, the need for these services arises from a desire on behalf of treating practitioners to respect individual autonomy. This is often a difficult task in ICU when patients cannot communicate easily. CONCLUSIONS Jehovah's Witnesses are uncommon in ICU but are not over- represented when compared with their prevalence in the community. Given the rarity of this patient population in ICU, we suggest that it would be prudent for referral centres \to have protocols in place to assist with management issues. A review of the literature indicates that from the beginning of their ICU stay (and weeks in advance with elective surgery), all JW patients should have a management plan to limit blood loss by minimizing the frequency and amount of venepuncture, instituting early and definitive surgical management, and using systemic anti- fibrinolytics when relevant. The early use of rHuEpo and iron supplements may prevent the later falls in haemoglobin that become critical in selected patients. This study found a trend towards higher mortality in JW patients compared with the rest of the ICU population. JW patients with Hb of less than 20 g/l are extremely unlikely to survive. ACKNOWLEDGEMENTS We are indebted to Michael Bailey of the Department of Epidemiology at Monash University for performing the statistical analysis and to Ann-Marie McKenna and Clinton Kitt for collecting data on patients. REFERENCES 1. The Holy Bible. King James edition. Cambridge University Press. Acts 15:28-29. 2. Watchtower Bible and Tract Society. Questions from readers. Watchtowcr 2000; June 15:29-31. 3. Savarese D, Waitkus H, Stewart F, Gallery M. Bloodless medicine and surgery. Intensive Care Med 1999; 14:20-33. 4. Elder L. Why some Jehovah's Witnesses accept blood and conscientiously reject official Watchtower Society blood policy. J Med Ethics 2000; 26:375-380. 5. 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Transexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg 2000; 120:520-527. 31. Morgan G, Mikhail M, Murray M. Clinical Anesthesiology, 3rd Ed. McGraw Hill 2002:450. 32. Kirkley S. Proposed mechanisms of transfusion-induced immunomodulation. Clin Diagn Lab Immunol 1999; 6:652-657. 33. Vanvakas E, Blajchman M. Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction? Blood 2001; 97:1180-1195. 34. Ghio M, Ottonello L, Contini P et al. Transforming growth factor-β^sub 1^ in supernatants from stored red blood cells inhibits neutrophil locomotion. Blood 2003; 102:1100-1107. 35. Hebert P, Wells G, Blajchman M et al. A multicentre, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340:409-417. G. MACLAREN*, M. ANDERSON[dagger] Intensive Care Unit, The Alfred Hospital, Melbourne, Victoria * M.B., B.S., F.J.F.I.C.M., F.R.A.C.P., Former Senior Registrar. [dagger] M.B., Ch.B., F.A.N.Z.C.A., F.J.F.I.C.M., Staff Specialist. Address for correspondence: Dr M. Anderson, Intensive Care Unit, The Alfred Hospital, Commercial Rd, Melbourne, Vic. 3004. Accepted for publication on July 12, 2004. Copyright Australian Society of Anaesthetists Dec 2004 | 
