What follows is my non-copyrighted summary of my approach to the psychiatric evaluation of candidates for organ transplantation. I don’t consider myself a transplant psychiatrist and I very seldom conduct these assessments nowadays. You should not take my word as gospel and always consult your physician about any matter concerning health care. The content in today’s post is not intended as medical advice. The post is intended for educational, informational, and discussion purposes only. It is definitely not intended to direct the care of individual patients, but to highlight the assessment and management challenges associated with psychiatric consultation requests regarding psychosocial evaluation of organ transplant candidates.
This was prompted by resident psychiatrists who recently notified me that trainees are being asked to conduct these types of evaluations on an emergency, on-call basis. I happen to think this is not the optimal way to approach this extremely complicated, emotionally charged, and non-entry level consultation. If these are being done by resident physicans on the weekends and in the middle of the night then telephone support at the very least by a faculty psychiatrist with experience in transplant psychiatry should be available. If you’re a regular reader of my blog, then my ambivalence about further subspecialization in Psychosomatic Medicine is well known, based on my posts about American Board of Psychiatry and Neurology requirements for Maintenance of Certification and the Performance in Practice modules. However, in my view, if another subspecialty approval process is ever considered, transplant psychiatry would be at the top of my list.
Psychiatric Assessment for Organ Transplant
Typical Consult Question: “Is the patient able to comply with post-transplant regimen and what is the risk for relapse to substance abuse?”
These consultation requests come from multidisciplinary transplant center teams and can be non-urgent or as part of an emergency work-up, e.g., for patients in fulminant liver failure as a
result of acetaminophen poisoning. In the latter, the consulting transplant psychiatrist is often expected to be on call 24/7, making it necessary to saddle up and get over to the hospital as quickly as possible.
Organ transplant is one of the most challenging areas where Psychosomatic Medicine specialists practice. Some historical background follows:
- 1954: First whole organ transplant between identical twins (living donor)
- 1977: A computer-based organ matching system was established in the United States: the United Network for Organ Sharing
- 1983: Introduction of cyclosporine, and later other drugs, which modulate immunosuppression.
- Since then, demand for organs is steadily increasing.
- One of the current challenges in the field relates to the shortage of organ donors.
- 2001: The UNOS database recorded that the total of living donors exceeded the number of deceased organ donors.
- Legislation regulates the donation of organs.
The number of persons needing organ transplant far exceeds the number of available organs. Annually, 10%-15% liver, heart, and lung transplant candidates will die while on the wait list. Graft survival rates are lower than patient survival rates; therefore many will need a second transplant.
The patients most often at the center of requests for consultation can suffer from many kinds of psychological distress which include the stress of living with end organ failure, being on the transplant wait list, complications of medical and drug treatments, pre-existing psychiatric disorders, and pre and post transplant issues often including but not limited to adjusting to complex medical regimens
and lifestyle changes.
The most frequent question that consultees from the transplant team ask is whether the candidate is a good risk for receiving an organ that is in short supply, which therefore must be allocated carefully, and of which the candidate must be prepared to be a good steward. Psychosocial screening is a feature of most transplant programs. Rather than seeing ones self as a gatekeeper, most experts agree that the most useful part of the psychosocial screening process is to identify psychosocial factors that would interfere with the candidate’s successful adaptation to life posttransplant, and to develop a plan for managing them using available resources.
The best way to conduct pretransplant evaluations is a subject of debate and many transplant centers find creative means of approaching the problem. Large numbers of candidates can preclude comprehensive psychiatric consultations for each patient. At a high-volume transplant center, this might lead to the use of patient-rated screening batteries, which can identify those at higher risk for psychiatric challenges to address.
The most pressing question that our colleagues have in transplant surgery is whether we can predict compliance with posttransplant medical regimes and remain abstinent from substances Immunosuppressant non-compliance tends to be highest in kidney transplants, failure to exercise highest in heart recipients, and pretransplant substance abuse predicts posttransplant use that frequently compromises transplant success. However, the weak correlations between psychosocial factors and nonadherence, according to some authors, suggest that provider-related and systems-level factors may be more influential than previously thought. Most of the recent published research indicates that it probably doesn’t make much sense and is ethically problematic to apply a rigid requirement of 6 months of sobriety from alcohol by candidates for liver transplant[5, 6]. However, a recent meta-analysis concluded that there were only three factors modestly associated with posttransplant outcomes: poorer social support, a family history of alcohol abuse/dependence, and a pretransplantation duration of abstinence of 6 months or less all mildly increased the risk for posttransplant relapse. The authors are quick to point out that, although they are statistically significant, they are “not strong enough to predict risk with a high degree of accuracy.”
The consulting psychiatrist must weigh the duty to several stakeholders:
- The transplant candidate
- Other patients on the transplant waiting list
- Living related donors if they are viable alternatives to cadaver organ transplantation
- Society in terms of husbanding the scarce resource of cadaver organs
- The transplant service, which must have an acceptable survival rate of patients transplanted in order to retain accreditation status
The evaluation process is more difficult because of competing expectations from the stakeholders. For example, the transplant candidate and his family may believe that he is entitled to the organ, and they are both keenly aware of one of the alternatives to not being approved for transplant—death. This may lead to what has been called “impression management”, a euphemism for strategies to enhance the candidate’s suitability for transplant which may or may not include lying. The number of persons needing transplant far exceeds the number of available
organs. The transplant surgeon may harbour a belief that it is the transplant psychiatrist’s role to act as a gatekeeper in order to screen out those with psychosocial background histories that might predict poor post-transplant outcomes. These are only two of the many factors that can affect a process that frequently arouse strong emotions. Doctors, like many professionals, are poor lie detectors.
A recent literature review reveals continuing support for the prevailing opinion that, until further data is available, that the so-called “6 month rule” of requirement for abstinence “in most cases provides a safe and prudent means of ensuring that an individual with ALD is an appropriate candidate for liver transplantation”.” However, they also acknowledge that strict enforcement of the 6-month rule would unfairly punish those who may die before the achieving the 6 month eligibility criterion. Dimartini, et al are very clear on their opinion, frankly stating that the notion that a short length of pre-liver transplant sobriety can guarantee post-transplant sobriety “is misguided.” Long term studies show that stable sobriety is measured in years, not months. In their study, a specific
length of pre-transplant sobriety that predicted abstinence could not be found.
About 10%-20% of patients transplanted for ALD relapse to alcohol after transplant. According to Lim, “Surprisingly, little evidence exists to document a significant detrimental effect on graft or patient survival associated with resumption of drinking”. However, in the setting of comorbid Hepatitis C, alcohol relapse can be particularly deleterious, leading to rapid progression of recurrent Hepatitis C infection, cirrhosis, and worsening graft and survival outcomes.
A large study found that rejection episodes in heavy drinkers were directly related to poor compliance with immunosuppressives, with 3 of 7 deaths among this group directly attributable to alcohol relapse. Dimartini, et al reported that “…predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation’. Outcomes beyond 5-7 years are poor, and may be related to ongoing smoking and immunosuppression linked to vasculopathy and cancers.
There are a couple of prospective studies that systematically examine the impact of psychiatric risk factors typically included on psychiatric pre-transplant evaluations. The Owen study found that previous suicide attempts, poor adherence to medical recommendations, previous drug or alcohol rehabilitation, and depression significantly predicted attenuated survival times. Past suicide attempt was associated with greater risk for post-transplant infection. Shapiro et al found that several pre-transplant risk factors were associated with post-transplant adherence problems: substance abuse, unstable living arrangements, and personality disorder among them. None were significant predictors of post-transplant infection or survival. However, Dew et al showed that poor adherence to post-transplant medical regimens substantially increased risk of acute graft rejection and cardiac allograft disease.
The sample evaluation form that can be used as a guide by psychiatric consultants is adapted from Klapheke below:
i. Patient name and hospital number, date
ii. Identifying information and reason for the consult
iii. Purpose of consult explained to patient and consent obtained
iv. History of present illness
- Emotional and cognitive preparedness for transplant a. Attitude and motivation for transplant
b. Has an understanding of
i. Waiting period for transplant?
ii. Length of hospitalization and recuperation?
iii. Risks and benefits of immunosuppressants
iv. Comfortable with acceptance of donor organ?
v. Expresses commitment to comply with post-transplant care (understands and signs a post-transplant care commitment agreement or contract)?
vi. Previous coping strategies for dealing with stress (active versus avoidant, for example)?
vii. Realistic expectations regarding post-transplant functioning?
v. Psychiatric and substance abuse history
vi. Medical history
- Major medical problems
- Current medications and allergies
- History of compliance with medical treatments.
b. Complies with medications and diet regimen?
c. Able to develop working alliance with treaters?
d. History of leaving the hospital against medical advice?
vii. Family psychiatric history
viii. Social history, including
- Employment, legal, military, marital
- Current stressors and support systems
ix. Review of systems, pain assessment
x. Mental status examination
Psychosocial rating scales are also used. The Psychosocial Assessment of Candidates for Transplantation (PACT) is an example. It was developed in the 1980s, and the results of a study of its reliability
published in 1989. The scale was never really intended to be used as a tool for candidate selection. Its original purpose was for studying the pretransplant psychosocial evaluation process itself and for learning how different programs weight various factors in patient selection.
The Transplant Evaluation Rating Scale (TERS) is another psychosocial rating scale that was also developed as a research instrument, though was used as a selection tool. The TERs also showed good
interrater reliability but was thought to be more cumbersome to use than the PACT[15, 16].
The newest rating scale is the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). It was developed by Dr. Jose Maldonado, MD, FAPM and colleagues at Stanford and he
presented the instrument at the Academy of Psychosomatic Medicine (APM) annual meeting at the November 2008 annual meeting in Miami. The group determined minimal listing criteria and it’s obviously intended to be used as a selection tool. It’s an 18 item scale being validated against the PACT. An interrater reliability study was under way at the time of the workshop at which the SIPAT was discussed.
Clinical decision-making and treatment
Most expert transplant psychiatrists promulgate the idea that the evaluation should have as its primary goals the identification of psychiatric challenges that might interfere with positive post-transplant outcomes, and the formulation of plans to cope with those challenges using available mental health resources. This approach enables the transplant center to evolve beyond the gatekeeper model, which can make the process seem focused on making judgments about a candidate’s social worth, which in turn can make the physician-patient relationship adversarial.
The formulation, diagnostic assessment and plan for helping the patient and the transplant team cope with any psychosocial challenges necessitates an understanding of current research regarding psychosocial predictors about transplant outcomes. The consultant should list the multiaxial diagnoses and deliver an opinion about the candidate based on the evaluation gathered from the clinical interview, information from collateral sources of history, and the medical record.
- Does the patient have the psychological and cognitive ability to:
a. Understand information and use a rational process to make an informed decision about treatment?
b. Adhere to a complex medical regimen?
2. Is the social support system adequate?
3. Is there a satisfactory history of adherence to medical treatment recommendations?
4. Does the patient demonstrate adequate emotional and cognitive preparedness for transplant?
5. Are there any other concerns regarding the patient’s candidacy?
The evaluation phase is critical to diagnosis of major psychiatric problems and to treatment planning for evidence-based interventions. However, providing follow-up through the other phases of transplant allow optimizing the development of a therapeutic alliance to foster adherence to both psychiatric and medical treatment and further evaluation of psychosocial challenges as well. The
waiting phase is a very stressful time and often the candidate must tolerate deteriorating health while watching others transplanted sooner. In the post transplant period, about 20% of patients develop any psychiatric disorder, most notably depression and PTSD. Pretransplant depression is not necessarily associated with poorer survival though PTSD might be[18, 19]. Treating with evidence-based
pharmacotherapy and psychotherapy is effective.
Cognitive disorders including delirium are a common problem in both pretransplant and posttransplant patients. They can result from end-organ disease, comorbid diseases, previous substance abuse, brain injuries such as stroke, and medication side effects. It’s critical to recognize delirium whenever it occurs because it’s potentially reversible. The major features of delirium are acute onset (often over hours to days), waxing and waning alertness, fluctuating symptoms over hours to days, disorientation, disturbed sleep-wake cycle, and clouding of consciousness. Patients may display fragmented delusions and perceptual distortions including frank hallucinations that are often visual. Mood and personality changes are also not uncommon.
A diligent search for reversible medical causes of delirium must be undertaken. They can range from hypoperfusion and hypoxia in heart failure to hepatic and uremic encephalopathy in liver and kidney failure. Interventions include attempting to normalize the disrupted sleep-wake cycle and scheduled dosing of antipsychotic while treating the underlying medical problem. Haloperidol in low
doses or atypical antipsychotic can be used. It is necessary to monitor the EKG periodically with Haldol, which, particularly when given IV, may cause QTc prolongation. A QTc >450 – 500 ms may increase risk of torsades de pointes. However, in atrial fibrillation, the QTc may not be a reliable marker to monitor. Side effects include rigidity, cogwheeling, tremor, somnolence, psychomotor slowing, and tardive dyskinesia. Neuroleptic malignant syndrome is rare, but a medical emergency. Symptoms are rigidity, fever, mental status changes, vital sign instability, leukocytosis, marked elevation of CK. Stop Haldol if these occur. If the patient receives Haldol IV, there needs to be cardiac monitoring per hospital protocol.
Although a recent review indicates that total daily doses over 35mg are more often associated with torsades de pointes, much higher doses have been used safely in ICU settings for management of delirium. If the QTc is above 450ms, use Haldol, especially IV, with caution. If the baseline QTc is prolonged, would be more cautious about using haldol if QTc becomes elevated above 25% of baseline, and one should consider discontinuing haldol if T-wave flattening or U wave development occurs. Monitor electrolytes, especially potassium, magnesium, and calcium, correcting to normal. Check for hypothyroidism (TSH with free T4 if elevated) as hypothyroidism is associated with torsades de pointe. Haldol associated torsades de pointe occurs in a small minority of all patients treated.
Both Risperidone and Olanzapine are available in oral disintegrating forms for patients who have trouble swallowing but who still have a functioning gut through which the drugs must be absorbed. Atypical antipsychotics can worsen hyperglycemia and hyperlipidemia, to which transplant patients can already be vulnerable from immunosuppressive medications. Medications that can cause delirium in transplant patients include calcineurin inhibitors like Tacrolimus and Cyclosporine as well as corticosteroids.
Many complex transplant issues are dealt with in the ICU, but it’s often not clear where to manage those with both medical and psychiatric problems. These patients are often too medically sick to be cared for safely on a general psychiatric inpatient unit yet are often behaviorally too challenging for nursing staff on medical or post-surgical units. This population could be ideal for Complexity Intervention Units (formerly Medical-Psychiatry Units (MPUs)) in order to add value to patients and reduce total cost for health care organizations. They contain both medical and psychiatric safety features and are staffed by nurses and physicians with combined medical and psychiatric training.
The use of Lithium and Divalproex for the treatment of mania is not recommended in transplant patients generally because of the propensity for large fluid volume shifts and diuretic use as well as liver toxicity respectively with these agents. Atypical antipsychotics can be used to control mania and primary psychosis as long as one remembers the risk for hyperglycemia and hyperlipidemia.
Both anxiety and depression are relatively safe in the transplant population, though Fluoxetine, Paroxetine, and Sertraline may be more likely to be associated with drug-drug interactions which could lead to toxicities. Fluvoxamine and Nefazodone have very significant interactions with calneurin inhibitors and should be avoided.
Immunosuppressive medications can cause neuropsychiatric side effects. The calcineurin inhibitors (Tacrolimus and Cyclosporine) can cause tremor, restlessness, insomnia, vivid dreams, anxiety, agitation in about 50% of transplant recipients. They have also been associated with the development of a complex neuropsychiatric syndrome, Posterior Reversible Encephalopathy Syndrome (PRES).
Corticosteroids are also associated with psychiatric symptoms, especially when used in doses of 40mg of prednisone-equivalent and above. A variety of reactions occur, including anxiety and mood changes on up to delirium and psychoses.
An innovative way to manage psychosocial treatment delivery in areas where many transplant recipients live at a distance from the transplant center was developed by Dew and colleagues. They designed a Web-based intervention for heart transplant recipients that included stress management, medication management, and access to electronic communication with the transplant team.
Mental health and quality-of-life benefits were greater for the intervention group who used it more frequently.
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