Australasian Anaesthesia 2011 - Australian and New Zealand ...

94 Australasian Anaesthesia 2011Care of the potential lung transplant donor – optimisation, prevention of decline and future prospects. 95DONOR AGELittle evidence exists to support a specific upper age limit however older donors of kidney, heart and liver are wellestablished as associated with lower graft survival and it is unlikely that lungs are not similarly affected. De Perrotet al in Toronto have shown higher rates of bronchiolitis obliterans syndrome (BOS) in recipients of older grafts. 7Generally older donor lungs are used for older recipients when possible. It is thought that older lungs may be lessimmunologically active however the older donor tolerates ischaemia less well than younger donors. The InternationalSociety for Heart and Lung Transplantation (ISHLT) data registry supports this in their current guidelines. 6ARTERIAL BLOOD GASThe minimum of 300 for PaO 2 :FiO 2 appears to have been accepted as standard based on one case report from1987. This report showed a single case of graft failure where the preoperative donor ratio was less than 250. Sincethis case, the ratio of 300 has been adhered to without further evidential testing.Multiple factors exist in the critically ill and brain dead patient to impair the ratio. Aspiration, atelectasis, neurogenicpulmonary oedema (NPO), sepsis and fluid management all can impair gas exchange.CHEST RADIOGRAPHA clear chest radiograph (CXR) has been included in current ISHLT recommendations despite this being a weakestimator of abnormalities.CXR may be an indicator of aspiration, fluid loading, pulmonary oedema, sepsis or structural abnormality/trauma.Inter observer error is significant with regard to this reporting and may be done out of normal hours by non radiologyclinicians. Unilateral infiltrates are likely acceptable whereas diffuse bilateral infiltrates have a higher rate of primarygraft dysfunction. Currently there is no clear evidential basis on what CXR findings are acceptable. The marginalCXR is best considered in combination with other criteria.BACTERIAL COLONISATIONBronchoscopy is performed prior to initiating the donor procedure. Presence of gross inflammation or purulencegenerally precludes lung donation. Sterile secretions are uncommon so a quantitative assessment by the donorprocurement team of secretion load is usually undertaken. Microbiological specimens are taken that may help tailortreatment should infection become established in the recipient. Length of time on mechanical ventilation influencescolonisation of the tracheobronchial tree; however no absolute time limit exists for exclusion. Most important is themanagement of the patient whilst ventilated. This will be discussed in further detail later.Bacterial infection is not uncommon in the recipient but carries a lower risk than viral or fungal infection. Currentguidelines do not include the routine administration of antibiotics as part of the donor procurement however manyteams employ broad spectrum antibiotics immediately prior to retrieval. Given the weakness of predicting VAPbased on CXR compared to histology this seems prudent. If unilateral infection exists, this does not preclude singlelung transplant should there be a suitable recipient.GRAFT ISCHEMIC TIMEIt is endeavoured to maintain the time from donor aortic cross clamp to reperfusion as short as practically possible.Cold ischemic times are ideally less than 6 hours. Again however, little evidence supports this arbitrary time.Combined age over 55 and longer ischemic times do have increased one year mortality but considered alone,prolonging times does not influence early graft function or long term mortality. The upper limit has not beendetermined, case reports of times as long as 11 hours exist. It is possible that with new developments such asex-vivo lung perfusion that longer ischaemic times will become more common.THE PATHOPHYSIOLOGY OF BRAIN DEATH AND ITS EFFECTSBrain death testing is outlined in the document “The ANZICS statement on death and organ donation”. A .pdf checklist is available to clearly record this. 8 Injury to the neuron results in loss of membrane function. As a consequence,the neuron cannot maintain its internal homeostasis and oedema will develop within the neuron. The more severethe injury, the greater the oedema that will develop. As the cranium is non elastic, the rise in brain tissue volumemust be at the expense of blood and cerebrospinal fluid volumes, the so called Monro-Kellie doctrine. Onceintracranial compliance limits are reached, intracranial pressure rises. Cerebral blood flow falls as intracranialpressure rises, further worsening cellular oedema. Once intracranial pressure has risen above mean arterial pressure,perfusion pressure will be zero and blood flow to the brain will cease. Further oedema will develop resulting incompression of the brainstem with subsequent brainstem death.HEMODYNAMIC CHANGESCompression of the brain stem occurs in a rostral to caudal progression. Pontine compression and ischaemia leadsto a Cushing reflex, hypertension with bradycardia due to mixed sympathetic and reflex vagal discharge. Asischaemia progresses further, the medulla oblongata is rendered ischaemic with loss of the vagal nuclei causingunopposed sympathetic tone, the “sympathetic storm” of hypertension and tachycardia. Progression of ischaemiathen involves the spinal cord with loss of all sympathetic tone, complete vasoplegia and cardiovascular collapse.The sympathetic stimulation may reduce coronary perfusion through vasoconstriction and cause contraction bandnecrosis of cardiac myocytes. 9 There may be multiple arrhythmias and significant ST-segment changes compatiblewith strain or ischaemia.PULMONARY EFFECTSSevere pulmonary effects can occur during the sympathetic storm. NPO is a common consequence and has asignificant effect on gas exchange. It is a major cause of lung donor unsuitability. Intense systemic vasoconstrictionraises systemic vascular resistance (SVR). This shifts the systemic blood volume (usually 76%) to the pulmonarycompartment, raising it from 24 to 72% of total blood volume. 10 The rise in both SVR and left atrial pressure (frompulmonary volume loading) may lead to acute severe functional mitral regurgitation, possibly made worse bymyocardial ischaemia. Right ventricular work elevates and it may become volume overloaded. The rapid rise inpulmonary capillary hydrostatic pressure results in endothelial leak and alveolar oedema.A separate mechanism is also known to contribute to NPO. Direct alpha stimulation of the pulmonary circulationdespite pulmonary normotension can cause capillary leak and alveolar oedema. It is unclear which of these twomechanisms dominates, however the end result is pulmonary oedema and impaired gas exchange. Patients withcomplete high cervical cord injury may manifest less severe pulmonary injury due to loss of direct neuronal pathways.The speed of brain stem death or “coning” may also influence the intensity of the sympathetic storm. When coningis rapid, the effects may be more severe.SYSTEMIC INFLAMMATIONBrain death results in a systemic inflammatory response with rises in acute phase cytokines, particularly IL1β, IL6and IL8. These cause neutrophil aggregation and activation and mediate endothelial and alveolar injury. Whilstthese cause direct organ injury, possibly contributing to organ non acceptance, they are also associated withincreased early graft dysfunction in the recipient. 9COAGULOPATHYBrain death may also be associated with exposure of tissue thromboplastin to the circulation due to disruption ofthe blood brain barrier and endothelial dysfunction. This activates the coagulation and fibrinolytic cascades andmay result in further lung injury.ENDOCRINE FAILUREThe hypothalamic pituitary axis may also be affected by brain stem death. Significant hormonal derangementscontribute to further cardiovascular decline. Anterior pituitary function is less commonly affected than posterior.More commonly, in up to 80% of donors, there is severe depletion in posterior pituitary hormones, i.e. those ofhypothalamic origin. Most significant haemodynamically is the fall in antidiuretic hormone (ADH) which also contributesto diabetes insipidus (DI). DI is present in 80 to 90% of donors post brain death. Antidiuretic hormone expressioncauses aquaporin channel insertion into the collecting ducts of the distal tubule. This prevents water reabsorptionand results in large volumes (>1L/hr) of dilute urine being passed. The effect of this is hypovolaemia, hypernatraemia,hypomagnesaemia, hypophosphatemia, and hypocalcaemia. This should be differentiated from diuresis causedby mannitol or diuretic therapy. Correction should not be delayed by waiting for serum and urine osmolality results.Hypernatraemia is important to correct as it is associated with impaired outcomes in both liver and kidneytransplantation.Anterior pituitary impairment may result in falls in thyroid and corticoid hormones.The fall in thyroxin, cortisol and insulin levels is associated with a shift from aerobic to anaerobic metabolismand rises in serum lactate and hydrogen ion levels. Various studies have been performed looking at hormonereplacement therapy. These will be addressed later.HYPOTHERMIABrain death results in loss of upper motor neurons and vasomotor tone so there is an inability to conserve heat andshiver. There is reduced muscle and brain metabolism. Hence, hypothermia is a common feature. This may haveadverse effects on coagulation, oxygen delivery (left shift of the oxyhaemoglobin dissociation curve reducesperipheral oxygen unloading from haemoglobin), arrhythmias and end organ function. Forced air warming blankets,fluid warmers and humidified ventilator circuits are useful adjuncts to maintain normothermia.MULTIFACTORIAL LUNG INJURYOther events may contribute to pulmonary dysfunction. Events leading to brain death such as aspiration prior toand during attempted airway protection, atelectasis and cardiopulmonary resuscitation (CPR) causing pulmonarycontusion will worsen lung injury, function, and increase infection risk. Micro aspiration can occur around endotrachaeltube cuffs despite appropriate inflation.Whilst receiving invasive ventilation, still further injury is possible. Volutrauma and barotrauma are possible fromventilator management leading to ventilator associated lung injury (VALI). Intentional hypocapnea achieved throughhyperventilation as a therapy for intracranial hypertension uses high tidal volumes (10-12ml/kg) and respiratoryfrequency, both of which are associated with VALI.Gastric decompression via oro or nasogastric drainage may reduce reflux and pooling in the hypopharynx andalso improve ventilator mechanics. Ventilator acquired pneumonia (VAP) is increasingly likely with prolonged invasiveventilation. VAP incidence is approximately 1-3% per day ventilated.