Critical Care of the Transplant

Patient

Dr. Liesel Bösenberg

Specialist Physician

Fellow in Critical Care

Kalafong Hospital & SBAH

Organ, organ on the wall, what to we do if

you fail us all?

• Aim of talk is to give broad overview on this topic

• Solid organ transplants:

• Liver transplant patients

• What‟s up with the kidney

• Heart , lung and heart-lung transplant

• The bone marrow

Liver transplant patients:

Managing complications related to ESLD:

Cerebral function and encephalopathy

• Seen in acute and acute-on-chronic liver failure

• Ranges from delirium to coma

• Development in patients with cirrhosis poor

prognostic sign with 1-year survival <42%

• HE is a clinical diagnosis

Pathogenesis of HE:

• Increased Ammonia due to hepatic dysfunction and

porto-systemic shunting

• Ammonia metabolized to glutamine which leads to

astrocyte swelling and glutamine-induced

mitochondrial dysfunction

• Cerebral oedema and intracranial hypertension

• Underlying sepsis or GIT haemorrhage are

important precipitants for acute decompensation

• After OLT calcineurin inhibitors may lower threshold

for convulsions and alter LOC

Management of HE:

• Treat precipitant and support organ systems

appropriately

• Intracranial pressure monitoring not recommended

in these patients

• Manage GIT haemorrhage , SBP etc.

• Lactulose 45ml per NG until evacuation occurs then

enough to achieve 2-3 soft movements per day

• It is a non-absorbable dissaccharide that acidifies

the colonic lumen and has an osmotic cathartic

effect

• Lactulose enemas for severe HE

Treatment of HE

Screening and treatment of infections:

• Pneumonia and SBP in 20-40% o cirrhotic patients

admitted to ICU with sepsis

• „immunocompromise‟ in cirrhosis result of

decreased macrophage clearance, deficiency in

complement reactions and down regulation of the

monocyte human leucocyte antigen- DR expression

• Monocytes also have decreased expression of Il-10

• Sepsis in cirrhosis overwhelming pro-inflammatory

component

• Organisms to watch out for MRSA, VRE,

Acinetobacter

Cardiovascular:

• Hyperdynamic circulation with a low SVR,

increased Q, low normal or decreased systlic

arterial BP

• Splanchnic and systemic vasodilatation and renal

vasoconstriction

• Up regulation of RAAS system, increased

sympathetic drive

• CAD in 20-30% of these patients

• HD management in sepsis- unknown if targets need

to be modified in ESLD

• Norepinephrine, vasopressin , extracorporeal

albumin dialysis , hydrocortisone

Hepatopulmonary syndrome and

portopulmonary hypertension

• HPS = liver cirrhosis, abnormal pulmonary gas exchange, intrapulmonary vascular dilation, resolution in up to 80% post-transplant

• Severe hypoxia due to vascular shunt

• Mortality is 16% at 19 days and 38% at one year

• Orthodeoxia and platypnoea

• PPHT = portal hypertension with pulmonary hypertension, in 20% of pretransplant patients

• Response to epoprostenol ( PGI2 analogue)

• Mechanical ventilation according to ARDS protocols, PEEP 5-12 cmH2O

Associated renal dysfunction: HR syndrome

• Pathophysiology relates to intense renal

vasoconstriction secondary to SNS activation as a

response to splanchnic vasodilatation due to

increased nitric oxide production in portal

hypertension

• Hallmark is a low u-Na

• Type 1 and Type 2

• Best studied therapy is albumin 1mg/kg plasma

volume expansion then 20-40g/day for 14 days

• Also octreotide 100-200 g SC tds

• Also use alpha agonists to increase BP

Delisting happens…

Post liver transplant: Post reperfusion

syndrome:

• Poorly understood- happens when there is

reperfusion of the portal vein through the donor

graft

• Hypotension, bradicardia, vasodilatation, pulmonary

hypertension, hyperkalaemia and sometimes

cardiac arrest

• Resolves with fluid loading and electrolyte

management

Post-op care: early complications:

• Technical

• Complications related to existing liver disease

• Complications of the immunosuppressive agents

• Graft function

• Monitoring graft function in ICU:

• General parameters:

• Liver perfusion, bile production, haemodynamics

• Coagulation : INR and the prothrombin time

• Biochemistry: glucose, gases and lactate

• AST, bilirubin, ALP/ GGT

CVS:

• Watch out for underlying cardiomiopathy

• After transplant hypertension with increased SVR

due to restoration of normal liver function and portal

pressures

• Calcineurin immunosuppressants also have

hypertensive effect, increased afterload may

unmask cardiac dysfunction

• Decreased miocardial contractility due to operation

related issues: prolonged caval clamping, acidosis,

haemorrhage and hypocalcaemia

Respiratory:

• Pleural effusions, ongoing shunting secondary to

HPS with resulting hypoxaemia

• Atelectasis

• Infections

• TRALI

AKI post transplant can happen:

Technical complications:

Graft failure: does anyone have another

donor? Primary non- function

Renal transplants:

Complications related to treatment

Complications in the grafted kidney

• ARF/ CRF

• Nephrotic syndrome

• Drug-induced

• Infection related

• Obstructive uropathy

• Acute obstruction of the transplant artery/vein

• Peri-transplant haematoma

• Urine leak

• Lymphocoele

Lung transplants:BLT/SLT

•Heart-lung transplants reserved for Eisenmenger

secondary to complex congenital heart lesions

The deenervated lung

• Lungs remain permanently deenervated

• Bronchial artery and lymphatic system regenerate

after a few weeks

• Regulation of breathing through chest wall afferents

and wean off ventilation within 48 hrs

• Bronchomotor tone is retained

• The cough response is lost under the anastomosis

Post-op:

• Implantation response within few hours

• Infiltrates on x-ray with peribronchial cuffing due to

lung oedema

• Management supportive with fluid restriction

• Hyperacute rejection: poor prognosis for recovery

• Early rejection: infiltrates and decreased PaO2 after

48-72 hrs: pulse steroids and antibiotics

• BAL and transbronchial biopsies

• Anastomotic problems- broncial/ tracheal stenosis

• Sputum retention

Ischaemia-reperfusion injury:

• Sign of early graft dysfunction

• Also called reperfusion oedema/ reimplantation response

• Incidence of 15-35%

• Native lung has elevated vascular resistance, high blood flow

to dysfunctional allograft and significant V/Q mismatch

• Can occur within 24 hours post-op, manifests with reduced

lung complience, altered gas exchange and hypoxemia

• 97% of radiographs show changes on day one compared to

100% on day 3.

• BAL and transbronchial biopsy might be necessary to

distinguish between infection and hyperacute rejection

Management of IR injury

• ARDS protocol

• PGE1 IVI

• Inhaled NO

• Pentoxifylline

• Inhaled prostacycline

• ECMO

Mx of SLT dysfunction:

• Small tidal volumes

• Tolerate moderate respiratory acidosis

• Lateral decubitis

• “New lung up”

• Bronchoscope

• ILV

Anastomotic problems:

Bronchus dehiscence:

• Suspected if large air leaks from IC drains

• Pneumomediastinum/ -pericardium

• Empyema

• Other mechanical compications include strictures,

stenosis and bronhcomalacia

Infections : Bacterial / viral/fungal

Hyperammonemia syndrome

• High mortality rate

• Severe onset of neurological dysfunction and

deterioration in the first 4 weeks following the

transplant

• High ammonia levels with discordantly low liver

function tests

• Metabolic stressors which lead to increased protein

turnover and a negative nitrogen balance include

allograft rejection , IR , acute GIT bleeding etc.

Long-term complications:

• Obliterative bronchiolitis sign of chronic rejection

• After 6 weeks: Infx with CMV , alsp repeated

pseudomonas and MRSA

• Complications related to immunosuppresive drugs

Heart transplants:

The deenervated heart

• Remember two P waves , resident SA node and

grafted SAnode

• No autonomic innervation - only drugs that act

directly on myocardium can be used

• Atypical response to exercise, hypovolemia and

hypotension

• Increase in Q if preload increases will be delayed

• Verapamil and nifedipine have enhanced effects in

the transplanted heart

• Adenosine can cause profound hypotension and

even asystole

• Amiodarone can cause hypotension

Management of immediate post-op

haemodynamic instability:

• Inotropic support ( milrinone/ epinephrine) for poor LV/RV contractility

• Pressor support ( norepinephrine) : low systemic arterial pressures despite good filling pressures and contractility

• Heart rate support with chronotropic drugs/pacing : intrinsic low gratfted heart rate ( milrinone/ isoprenaline)

• IABP : poor LV function not responding to other measures

• RVAD/LVAD/BiVAD

• Inhaled NO

• Resternotomy for bleeding/tamponade

Other complications:

• Infection, malignancy and graft atherosclerosis/ cardiac

allograft vasculopathy

• Infections:

• 45% bacterial and 10% fungal, mortality highest with fungal

• Malignancy:

• 1-2% risk per year

• Skin tumours and lymphomas

• CAV:

• Obliterative atherosclerosis

• Very diffuse, rescue therapy with angiographic interventions/

CABG very difficult

• Statins and Ca channel blockers might delay process

Multi-visceral transplants:

Hemapoetic stem cell transplants

Pulmonary complications:

• Engraftment syndrome:

• 7-35% of patients

• Develops within the first 96 hrs after transplant

• Fever, diarrhoea, erythematous rash, diffuse pulmonary infiltrates, renal impairment

• Mortality of 25%

• Responds fairly well to steroids

• Discontinue GM-CSF

• Diffuse alveolar haemorrhage:

• Progressive dyspnoea, fever and cough & hypoxaemia

• Usually older age, pre-transplant chemotherapy/whole body irradiation

• Bilateral peri-hilar infiltrates

• BAL- hemosiderin-laden macrophages

GVHD:

• Most common symptom is a skin rash

• Manifests in CVS as pericardial effusion

• Also in GIT- NVD and bleeding

• Intestinal perforation

• CT abdomen may show small bowel oedema

• Also neurological complications

• Low grade disease can be treated with steroids

Veno-occlusive disease of liver

• Seen in allogeneic transplants

• Thrombotic occlusion of small hepatic vessels

• Most likely the result of endothelial damage due to

chemotherapy

• Manifests with weight gain, oedema, ascites,tender

hepatomegaly, jaundice and liver failure

• Treatment includes tissue plasminogen activator/

anti- thrombin II concentrates

• Whole lecture on its own, good article

Drug interactions in transplant patients

Further reading