For “Intensive Care Manual”
Stephen Streat FRACP
Intensivist, Department of Critical Care Medicine
Auckland Hospital, Private Bag 92-024
Auckland 1003, New Zealand
Many intensivists at times have responsibility for the care of organ transplant recipients and have
seen the benefits of organ transplantation – one of the great medical successes of the late 20th
century1. Clinical results continue to improve, despite the increase in co-morbidity and case
complexity that has accompanied the increase in indications for transplant and decrease in
contraindications to it. This success has led to an enormous increase in demand for organ
transplantation while the number of available organs has increased much more slowly, resulting in
rapid growth of transplant waiting lists2. Many transplant centres have reported an increase in
waiting times and an unacceptable number of patients dying on the waiting list.
In the absence of clinical xenotransplantation, tissue engineering or effective artificial organs,
transplant programs continue to critically depend upon donated organs. This has led transplant
professionals to accept organs from donors previously considered marginal, to increase
transplantation from living kidney3, liver4 and lung5 donors and to vigorously champion endeavours
to increase cadaveric organ donation, including non-heart-beating organ donation6. There has been
comparatively less consideration to restricting access to waiting lists7.
[A] Responsibilities of the intensivist
Intensivists are in general supportive of cadaveric organ donation8, are responsible for the care of
dying patients and their families, and should therefore be obliged to provide leadership in organ
donation. This personal view is growing in intensive care medicine8-10 but is not yet widely
accepted. Intensivists must ensure that the processes involved in determination of death and
facilitation of cadaveric organ donation remain of the highest standard and are publicly seen to be
so. These processes include the care of the dying patient and their family, determination of brain
death, identification of the potential for organ donation to occur, offering the opportunity for organ
donation to the family, maintenance of physiological stability throughout the time until organ
retrieval, and aftercare for the family of the deceased, irrespective of whether organ donation took
[B] Care of the dying patient and their family
Intensivists are, in general, familiar with the care of the dying patient including the need to avoid
suffering and maintain patient dignity. The respect of the ICU staff for the humanity of the dying
person is perhaps most obviously expressed in the “patient comfort care” provided by the nursing
staff and the evident compassion of the staff for the family11.
The intensivist has a crucial role to play in the care of the family of the dying patient. It is important
to establish rapport with the family very early in the critical illness by way of a family meeting.
There may need to be several “bad news” meetings in the days to come. Such meetings should be
attended by whomever the family defines themselves to include, and by the intensivist and a
member of the nursing staff acting as a support role for the family (and perhaps by a chaplain or
social worker if the family wish). The role of “support person” should be kept separate from the role
of the “bearer of bad news”. These meetings should be held in a separate private room large enough
to accommodate all the participants, away from the bedside and with “protected time” against
interruptions. The intensivist should convey, with evident compassion11, an accurate account of the
sequence of events together with a realistic assessment of prognosis and the immediate care plan.
Presenting CT or other visual information may assist the family to understand. There should be time
to answer any questions that the family may have, and at the end of the meeting the intensivist
should ascertain that the family understand what has been said,11 and that they are in agreement with
the care plan. Ensuring that anyone who speaks with the family gives a consistent message is an
essential part of maintaining trust between the family and the ICU team – ideally only one
intensivist should speak with the family. This strength of the trust in the relationship will determine
the ability of the ICU team and the family to deal together with the difficult and painful issues of
withdrawal of intensive therapies (should that occur), the death of the patient and subsequently the
consideration of organ donation.
Perhaps the most problematic issue for intensivists caring for the patient dying with severe brain
injury concerns the timing of the decision to withdraw brain-oriented intensive therapies while
continuing that physiological support which preserves the possibility of organ donation in the future.
It is often appropriate to withhold or withdraw brain-oriented intensive therapies (e.g. CSF
drainage) when it is clear that death is inevitable. This must involve assembling definitive
prognostic information, obtaining consensus of those involved in treating the patient and acceptance
by the family that death is inevitable. A sedative-free clinical assessment of CNS function is an
essential part of prognostication. The possibility of future organ donation has no part in the decision
to withhold or withdraw specific brain-oriented therapies. This decision is guided by the ethical
principles of non-malfeasance and respect for autonomy12. Most patients have devastating brain
damage with some brain stem function, and many of them may never become brain dead. It is often
appropriate to progressively withdraw, in a dignified manner, all intensive therapies from such
patients, while continuing to provide “comfort care” to the patient and support to the family12.
During the period of sedative-free CNS assessment, some patients will suffer apparent loss of brain
stem function. However, a greater percentage of patients will have apparent loss of brain stem
function despite continuance of all available surgical and medical therapy. Brain-oriented intensive
therapies should be withheld pending formal assessment of brain death. In order to meet the pre-
conditions for brain death assessment13, extracranial homeostasis must be maintained, and these
conditions also preserve the possibility of organ donation in the future.
[B] Identification of the potential for organ donation to occur
Most ICUs admit patients with very severe brain damage where it is clear that the probability of
survival is low. The primary indication for such admission is to identify that subgroup of patients
who may survive and provide them with the necessary care to enable that survival. There are
situations where it might be thought that the chance of that recovery is so remote that admission of
the patient to ICU would not ordinarily occur. Some have advocated admitting such patients to ICU
solely to allow for the future possibility that organ donation may occur, with accompanying explicit
discussion with the family of this possibility14. Although it seems likely14 that such a utilitarian
approach might increase the number of organs available for transplant, ethical15, legal16 and
clinical15 objections to the practice have all been raised.
Organ donation is possible in most situations where brain death has been confirmed. The absolute
general contra-indications to organ donation are few and are absent in the majority of brain-dead
patients. They include situations where there is an unacceptably high risk of the transmission to the
recipient of malignancy or infection or where the function of the possible donor organs is likely to
be unacceptably poor. Extracerebral malignancies and certain infections (e.g. with HIV) are likely to
remain absolute contraindications but other donor factors (e.g. advanced age, recent bacterial
sepsis17, positive HCV18 or HBV18 serology) are no longer thought absolute contraindications.
Before deciding that organ donation is contraindicated on medical grounds, intensivists should
discuss the specific issue with the appropriate agency (donor co-ordinator or organ procurement
Similarly, the organ-specific contraindications to organ donation have reduced in recent years as the
outcomes of recipient transplanted with donor organs formerly considered marginal have been
found to be acceptable19. Finally, these contraindications vary somewhat between transplant centres
and continue to change in a more permissive direction. In general the presence of more than mild
chronic organ dysfunction or the development of severe acute organ dysfunction will likely
contraindicate donation of that organ. However, intensivists should discuss these organ-specific
issues with the donor co-ordinator or appropriate agency before deciding that a particular organ is
unsuitable for possible donation and subsequent transplantation.
In most jurisdictions an appropriate authority (e.g. a coroner or medical examiner) may legally
interdict organ donation under certain circumstances (e.g. homicide) and this issue should also be
clarified with the donor co-ordinator.
The donor co-ordinator will clarify with the transplant teams whether any organ donation is possible
and whether particular organs may not be suitable and the intensivist should provide the co-
ordinator with the necessary information (see Table 1) for these decisions.
Table 1. Information likely to be required by transplant teams
Age, sex, weight, approximate height
Previous medical history (including co-morbidity, surgery, medication, alcohol, smoking, illicit
drug use and allergies)
Detailed clinical history of fatal illness (including history of cardiac arrest, periods of
hypotension or hypoxia)
Current clinical status (including ventilatory and inotropic support and physiological
Current investigations (including blood group, arterial blood gases, chest x-ray, ECG, urea,
creatinine, electrolytes, glucose, bilirubin, transaminases, alkaline phosphatase and gamma
glutamyl transpeptidase, prothrombin ratio, activated partial thromboplastin time, haemoglobin,
white cell count, platelets and all microbiology results).
[B] Determination of brain death
This is a clinical responsibility of the intensivist and must be carried out according to appropriate
codes of practice or clinical guidelines (see Chapter 45). The determination of brain death20,21
involves several stages – firstly establishing the presence of a condition known to produce severe
and irreversible structural brain damage, secondly the exclusion of possible confounding factors and
finally the determination by two independent clinical examinations that there is profound
unresponsive coma and persistent absence of brain stem function. The examination and
determination of brain death should be documented in the medical record, which is facilitated by a
pro forma. In the circumstance where clinical examination is confounded (e.g. by barbiturate coma)
then absence of cerebral blood flow must be documented by angiography or other reliable
The fact of brain death and its medical and legal implications must then be conveyed to the family.
It is often difficult for families to accept brain death as death, given the life-like appearance of the
skin, the rise and fall of the chest and the warmth of the hands that are preserved by ventilatory and
circulatory support. For some family members, the opportunity to view the second clinical
examination for brain death, or the cerebral arteriogram when clinical examination is confounded,
may help them to understand and accept the final awful implication of this diagnosis. Intensivists
should be open to offering these options.
In the absence of organ donation, it is appropriate to remove ventilatory support at a time that allows
for family needs.
[B] Offering the opportunity for organ donation to the family
The differentiation9 of organ donation (an intensive care unit activity) from transplantation allows
for the consideration of many perspectives that are often not considered in transplant-oriented
publications. Organ donation is an activity that fundamentally modifies the human rituals
surrounding death, even death in ICU. Organ retrieval is a surgical procedure carried out in the
operating room and although this is done in a respectful manner with identical surgical processes to
those used on living people, it is nevertheless viewed by some22 as “mutilating”. Discussion of
organ donation is an emotionally intense activity involving a newly bereaved family and a health
professional, and requires very clear and sensitive communication. It takes place at a time when the
family members have only recently been told that their loved one has died and yet they must
consider the issue at this time of intense grief – there is no other time. Knowledge of organ donation
varies widely in the community and some families may not previously have known that organ
donation and transplantation take place. Similarly, both discussion of organ donation and
acceptance and willingness to be part of it vary widely in the community. There is greater in-
principle agreement with organ donation than either individual agreement or decision-making on
behalf of a loved one. Discussion of organ donation among families is often promoted as a way of
increasing organ donation rates with some evidence that it may do so. Some family members will
have strongly held views against organ donation based on personal religious or cultural beliefs22.
There are several “transplant-oriented cultural attitudes” concerning organ donation including the
notion that organ donation is the only possible positive outcome that can occur in the setting of
brain death23, that it is appropriate to refer to brain dead persons in a utilitarian way as sources of
organs for transplant24, that for many families organ donation can assist with easing the pain of loss,
and that fulfilling the previously expressed wishes of the donor should be the primary or indeed the
only25 consideration. In some jurisdictions these wishes have indeed been defined to be legally
sufficient for organs to be retrieved, and are often argued to be a means of increasing the organ
donation rate26 by excluding the family from the opportunity to prohibit organ donation and
“returning control to the individual”. Implicit in this “transplant-oriented culture” is the judgement
that to for a family to agree to organ donation is desirable and perhaps of greater moral value than
the contrary decision, particularly if organ donation was the previously expressed wish of the dead
person. This judgement implicitly denies the legitimacy of the close human relationship between the
family and the deceased to determine what should happen to their loved one after death27. It is
noteworthy that even in countries that legally allow the previously expressed wishes of the deceased
to determine whether organ donation may take place, usual practice continues to involve the family
and not to proceed against family objection. Furthermore, the impact on the deceased's family was
rated as the most important factor determining consent practice in one such study28, implying an
incongruity between the law and clinically acceptable decision-making under these conditions.
Intensivists should be aware of their own views on these matters, and indeed the views of others that
might discuss organ donation with family members. Whilst intensivists most often initiate
discussion of organ donation with families in Australasia8, this is often not so elsewhere. Whoever
undertakes this discussion should be skilled in communication with grieving people. An existing
relationship with the family, which has been established over the previous family meetings, can
make this discussion easier to initiate by the intensivist. Defining this discussion as “offering the
option of organ donation” rather than “obtaining consent” (or even “persuasion”29) is not coercive in
language and frees the intensivist to providing complete and unbiased information, support the
family in their decision-making and thank them for their decision, whatever that may be. The
intensivist must ensure that the fact of death is understood. Then there must be sufficient time for
the intensivist to inform the family of the option of organ donation and what it entails, to answer any
questions and if necessary to facilitate decision-making by the family. They may take into account
previously expressed wishes, previous family discussions, personal and family values and cultural
and religious beliefs.
This discussion must not be coercive. Language that is potentially coercive (e.g. “fulfilling the
deceased’s wishes”, “doing what he would have wanted”, “something good may come of this”) can
re-define the situation in terms of the family coming to fulfil the intensivists wishes and should be
avoided. Finally, some language is particularly insensitive (e.g. the use of the term “harvest” rather
than “organ retrieval” to describe the process of organ retrieval, or “the body” rather than the
persons name to describe the brain-dead person) when viewed from the perspective of grieving
families and should also be avoided30. The intensivist should facilitate the family spending time at
the bedside prior to organ retrieval. Some tests (e.g. echocardiography or coronary arteriography)
may be performed during this time and the family should be informed about the reason and
implication of these. The intensivist should ensure that the family is offered an opportunity to spend
time with the deceased after organ retrieval if this is desired.
[A] Maintenance of extra-cerebral physiological stability in brain death
Immediately prior to brain death there is usually a period of hypertension, tachycardia and
occasionally dysrhythmia, mediated by both autonomic activity and catecholamine secretion.
Pulmonary oedema, biventricular dysfunction and myocardial injury may develop but there is debate
about the implications of these for subsequent cardiac graft function31. If treatment of this
adrenergic phenomenon is thought essential then a short acting –blocker (esmolol) should be used.
Cardiac arrest can rarely occur during this phase, usually due to tachydysrhythmia, but is often
reversible. This hypertension is soon followed by hypotension, associated with marked reduction in
sympathetic activity and catecholamine secretion. The hypotension may be profound in the presence
of simultaneous hypovolaemia or cardiac dysfunction and can lead to cardiac arrest or loss of donor
organ viability, and should be promptly treated by volume expansion and inotropic support.
Diabetes insipidus due to loss of ADH production soon follows and is manifest by brisk hypo-
osmolar polyuria, which will lead to hypovolaemia and hyperosmolality if untreated. Other hormone
abnormalities occur but do not have serious implications in the short term. Associated with the loss
of cerebral blood flow there is loss of cerebral metabolism and a fall of around 25% in oxygen
consumption and carbon dioxide production32. This leads to a fall in the necessary ventilatory
minute volume necessary for normocarbia. The fall in resting energy expenditure (heat production)
together with loss of vasomotor tone and the possibility of shivering-induced thermogenesis
exacerbate the risk of hypothermia developing.
Spontaneous movements and spinal motor reflexes may commonly persist in brain death33. These
rarely include bizarre movements20,34 which are often reproducible. Family members maybe invited
to view the second brain death test in order that there can be explanation of these responses should
they occur. Sympathetic responses may also occur to surgical stimulation and may justify the use of
anaesthetic agents in the operating room35.
[B] Suggested strategies for maintaining physiological stability
The onset of brain death is usually heralded by rises in intracranial pressure (if measured) or signs of
progressive loss of brain stem function (coma, pupillary dilatation) and the need for specific support
should be anticipated and planned for. This should include ensuring that central venous access is
available for inotropic support and perhaps measurement of central venous pressure, that additional
intravenous access is in place for rapid volume infusion and that a source of external heat (e.g. a
warming blanket) is available.
[C] Ventilatory management
The aims of ventilatory management are to maintain good oxygenation and normocarbia, minimise
circulatory depression and maintain, if possible, sufficiently good lung function to allow for future
lung donation to occur. The use of moderate tidal volumes (10-12 ml/kg) and addition of a low level
of PEEP (5 cmH20) may prevent atelectasis. Originally a PaO2 of more than 350 mm Hg on 100%
oxygen and 5 cm H20 PEEP was thought a necessary prerequisite criterion for lung donation but
recently PaO2/FiO2 ratios of 300 or 250 have been found to be acceptable36. Peak airway pressures
above 30 cm H20 should be avoided if possible. Usual pulmonary care including changes of position
and sterile endotracheal suctioning must continue. When pulmonary dysfunction is severe higher
levels of PEEP may be required to prevent airway frothing or provide adequate oxygenation. The
determination of apnea during brain death testing in such patients may require a period of
mechanical hypoventilation prior to apnea and continuation of CPAP during apnea in such patients
if serious hypoxaemia and circulatory depression are to be avoided.
[C] Circulatory management
The aims of circulatory management are to maintain adequate organ perfusion and arterial pressure
without producing fluid overload or excessive vasoconstriction, and without prejudicing future
cardiac donation. Reasonable initial haemodynamic goals include normotension (a mean arterial
pressure over 70 mm Hg), heart rate of 100 or less and central venous pressure of 8 mm Hg. Some
inotropic support is almost always required (e.g. 224 of the 237 donors in 2000 in Australia and
New Zealand37). Having established normotension with an inotrope infusion (noradrenaline,
dopamine or adrenaline), the haemodynamic response to a controlled volume challenge should be
The choice of inotrope has been the subject of much controversy but little evidence. Dobutamine is
largely ineffective and not recommended. The need for some pressor activity is common.
Noradrenaline (usually less than 500 g/h) is most commonly used in Australasia (67% of 224
donors in 2000 who received inotrope infusions37) without apparent detriment. Dopamine is less
commonly used and may exacerbate polyuria by its tubular effect. Adrenaline may have specific
benefit on renal blood flow in brain death38 but may also increase glycaemia and thereby osmotic
diuresis. Catcholamine infusion may reduce the up-regulation of organ immunogenicity that occurs
in brain death and lower the incidence of acute rejection in subsequent recipients of kidney grafts39.
Corticosteroids are sometimes used to improve haemodynamic stability, but their efficacy in this
setting is unknown.
Control of excessive polyuria will minimise the risks of developing hyperosmolality40,
hypovolaemia or hyperglycaemia secondary to infusion of large amounts of dextrose-containing
fluids. Synthetic desmopressin (1-D amino-8 D arginine vasopressin) is commonly given to control
diabetes insipidus and appears safe and effective37,41. In addition, low dose vasopressin infusion has
been shown to be safe and effective in reducing the amount of catecholamine required to support
arterial pressure42 without apparent detriment to subsequently transplanted organs. It should perhaps
be used in brain death if catecholamine requirements seem excessive despite adequate volume
Fluid therapy is similarly contentious. Control of diabetes insipidus is an essential aspect of rational
fluid therapy. Hypovolaemia should be corrected with resuscitation fluids. Haemoconcentration
occurs early after experimental brain death. Crystalloid infusion has been reported to worsen
pulmonary function in brain death and larger volumes will be required than if colloid is used43.
Although there is some evidence that hydroxyethylstarch may impair subsequent graft function in
the kidney recipient, this is debated44 and moderate volumes of starch are commonly given. There is
a suggestion of better preservation of renal function in sepsis with polygelin rather than starch but
the relevance of this situation to brain death is uncertain. At least moderate anaemia is well tolerated
in brain death but red cells may be given if needed to maintain packed cell volume around 0.25
pending organ retrieval. Free water should be given as necessary (1-2 ml/kg/hr as 5% dextrose) to
maintain serum osmolality in the range of 280-310 mosm/kg – corresponding to serum sodium
below 155 mmol/l. Severe hyperosmolality (probably a marker of inadequate donor care) is
associated with poor graft function in subsequent liver recipients40. Failure to control diabetes
insipidus will lead to increased requirements of free water to control serum osmolality. If 5%
dextrose is used for this then hyperglycaemia and osmotic diuresis may result.
[C] Metabolic management
Oxygen consumption, carbon dioxide production, heat production and glucose oxidation all fall in
brain death due to the loss of cerebral metabolic activity32. Hypothermia may easily develop in
association with vasoparesis, loss of shivering, exposure to room temperature, warm polyuria and
infusion of room temperature intravenous fluids. Core temperature should be kept above the 35–
36.5°C required to confirm brain death13,20. Keeping the ambient temperature high (24 °C) and
using infusion fluid warmers, heated humidifiers and external warming systems may be required.
Low dose insulin infusion is occasionally required to prevent hyperglycaemia. Serum potassium
should be kept above 3.5 mmol/l but potassium replacement should be given with caution as
hyperkalaemia is not uncommon and may be more easily produced after brain death. Unlike the
situation in sepsis, correction of hypophosphataemia does not improve haemodynamics in brain
death45. Although levels of thyroid hormones fall after brain death this is probably the “sick
euthyroid syndrome” and replacement of thyroid hormone does not improve the circulation after
[C] Non-heart-beating organ donation
Although some transplant centres, notably Maastricht47, have transplanted organs from such donors
for many years, non-heart-beating organ donation is being increasingly promoted. Immediate graft
function in recipients of such organs is often not as good as those of organs from brain dead
donors48 but long-term recipient outcomes may be equivalent. A number of centres have developed
conservative protocols for non-heart-beating organ donation and reported modest increases
(commonly 10-20%) in the total number of organs, particularly kidneys, available for transplant.
However, a cautious approach to non-heart-beating organ donation is still recommended as legal,
ethical and medical concerns remain49. Non-heart-beating organ donation should only take place in
the context of an institutional protocol wherein wide consultation has satisfactorily addressed these
[A] Aftercare of the donor family
The literature has focussed on the specific needs of the donor family and there may be specific
issues that need to be addressed, sometimes by way of a family meeting with an intensivist at some
later stage. Most organ donation agencies and transplant programs accept and facilitate limited
anonymous information being communicated between recipients and donor families but direct
contact is not recommended. However, routine aftercare for the families of all patients dying in
ICUs is increasingly recommended50. Such aftercare programs are well received11 and have the
potential to improve the care of subsequent families by revealing areas of inadequate or
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