9/30/2016 DaZed and COnFuseD Altered Mental Status Before and After Liver Transplant Kerry A. Decker, RN, MSN, ANP-BC September 30, 2016 Altered Mental Status Altered Mental Status • Change in level of consciousness • Infectious • Change in the level of awareness and the • Metabolic ability to focus, sustain, or shift attention • Organ Failure • Memory difficulties, disorientation, or speech • Neurologic Disorders that is tangential, disorganized, or incoherent • Psychiatric • Iatrogenic (Francis & (Francis & Young, 2014) Young, 2014) 1
9/30/2016 Altered Mental Status Altered Mental Status in Liver Patients in Liver Patients • Infectious Causes of Altered Mental Status in – Bacteremia/ Fungemia Patients with Cirrhosis – Sepsis • Metabolic – Electrolyte – Glycemic Hepatic Encephaphy – Nutritional Infection • Organ Failure Metabolic Disorders – Kidney failure: uremia – Liver failure: encephalopathy Drugs – Respiratory failure: Hypercarbia/ Hypoxemia Structural Lesions • Iatrogenic Psychiatric Disorders – Medication Other – Different environment – Irregular sleep patterns (Rahimi, Elliott & Rockey, 2013) Hepatic Encephalopathy Hepatic Encephalopathy: Diagnosis Hepatic Encephalopathy Precipitants in Patients with Cirrhosis Drugs Vascular Occlusion • History • • Benzodiazepines Hepatic vein thrombosis • • Narcotics Portal vein thrombosis • Physical Exam: • Alcohol Increased ammonia production or Portosystemic Shunting – Orientation absorption – Asterixis • • GI Bleed Placed shunts • • Infection Spontaneous shunts – Hyperreflexia • Metabolic Alkalosis Dehydration Primary HCC • Cultures • Vomiting • Labs: AMMONIA level not helpful • Diarrhea • Hemorrhage • Abdominal u/s with doppler • Diuretics (Ferenci, 2016) 2
9/30/2016 Hepatic Encephalopathy Hepatic Encephalopathy: Treatment Stage Description Neuropyschiatric Neurological Symptoms Symptoms • Identifying the underlying cause Minimal No evidence of LOC Measurable with No physical exam psychometric findings – Diagnose and treat infection testing Grade I Slight mental slowing Irritability; euphoria; Fine motor skill – Stop GI bleed Covert Decreased impairment attention span; – Correct electrolyte imbalance altered sleep – Stop narcotics and sedatives pattern Grade 2 Fatigue; apathy Slight disorientation Flapping Tremor, – Identify cancer or vascular occlusion to time Slurred speech Grade 3 Somnolence; confusion Marked Clonus, asterixis disorientation to Overt time and space Grade 4 Coma Unresponsive to - painful stimuli (Vilstru, Amodio, & Bajaj, 2014; Zhan & Stremmel, 2012) Hepatic Encephalopathy: Post Transplant Treatment • Lower ammonia levels – Lactulose • Initial treatment, and prophylaxis after an episode has occurred • Rectal vs PO • 30 gm Q1-2 hours until 2-3 bowel movements, then titrate to 2-3 bowel movements daily – Rifaximin • Recommended for hepatic encephalopathy refractory to lactulose • 550 mg PO BID (Vilstrup, Amodio, Bajaj, & Cordoba, 2014) – Polyethylene glycol • Small study of 50 patients randomized to either lactulose or polyethylene glycol demonstrated resolution of HE sx. (Rahimi, Singal, Cuthbert & Rockey, 2014) 3
9/30/2016 Small for Size Syndrome Altered Mental Status Defined • Infectious – Bacteremia – Fungemia Clinical syndrome defined by the presence of • Metabolic prolonged cholestasis, coagulopathy and ascites, – Primary nonfunction occurring when a partial liver graft is inadequate to – Small for size sustain metabolic demand in the recipient . • Iatrogenic – Medication Increased portal inflow leads to hepatic congestion • Steroids • Calcineurin Inhibitors (Alejandoro- Hernandez, 2016) Small for Size Syndrome Small for Size Syndrome Criteria Treatment Size and flow: • Decreasing portal inflow -Graft weight to recipient body weight ratio <0.8 & – Medically PVF>250 ml/min/100g • Octreotide 50-100 mcg/hr x 5 days – Surgically Two out of Four: • Shunt operation: mesocavl shunt, portocaval shunt and – Ascites splenorenal shunt • >1000 Ml on 3 consecutive days post op week 1 or on day 14 • Splenectomy • >500 ml on POD day 28 • Increase hepatic vein outflow – Hyperbilirubinemia – Surgically • >5 on 3 consecutive days post op week 1 or on day 14 • Include middle hepatic vein in right lobe grafts – Prolonged PT/INR • Hepatic Encephalopathy Tx • Uncorrected INR >2 on 3 consecutive days post op week 1 – Altered MS • Liver Growth • Grade 3/4 hepatic encephalopathy (Alejandoro- (Alejandoro- No other cause for the above Hernandez, 2016) Hernandez, 2016) 4
9/30/2016 Steroid Psychosis Steroid Psychosis Treatment Post-Op Steroid Dose • Steroid reduction Steroid psychosis may manifest as depression, mania, psychosis and delirium 0 (INTRA-OP) 1000 mg IV x 1 • Mood stabilizers and • Incidence is about 22% for neuropsychiatric events 0 (INTRA-OP) 500 mg IV x 1 • 2 fold risk of depression antipsychotic • POD 1 200 mg IV x 1 4-5 x risk of developing mania • 4-5 x risk of developing confusion POD 2 160 mg IV x 1 • Lithium • Increased risk with underlying psychiatric disorder POD 3 120 mg IV x 1 • Olanzapine • Psychotic symptoms are dose dependent. POD 4 80 mg IV x 1 • Haloperidol (Fardet, Petersen, Nazareth, 2012) POD 5 40 mg PO x 1 • Symptoms have been noted to develop in as little as 40 mg /day, but become • SSRI POD 6 20 mg x 7 days much more common at 80 mg/day • Fluoxetine POD 7-13 15 mg PO x 7 days (Boston Collaborative Drug Surveillance Program, 1972) POD 14-20 12.5 mg PO x 7 days • Diagnosis is largely based on history of exposure. POD 14-20 10 mg PO x 7 days POD 21-27 7.5 mg PO x 7 days (Brown & Chandler, 2011; Corbett, Nordstrom, Vilke, Thereafter 5 mg PO Wilson, 2016) Calcineurin Inhibitor Toxicity Calcineurin Inhibitor Toxicity Treatment • Acute alteration: May manifest as headache, tremor, neuralgia, neuropathy, – Removal of offending agent hallucinations, ataxia or seizures. – Try another CI • Incidence for neurological event – 10-28% with cyclosporine – see steroid psychosis – 21-32% with tacrolimus – 18% either • Seizures: • Recipients of liver transplant more affected than other transplant patients – Phenytoin • Predisposing factors may include: – Hepatic encephalopathy pre transplant – Levetiracetam – High MELD going into transplant – Lower hgb preoperatively • Headaches/Tremors: – Acute decompensation of chronic liver disease – Multiple surgeries -Propanolol • Not related to dose (Bechstein, 2000) ( Balderramo, Prieto, Cardenas, Navasa, 2011; Bechstein, 2000) 5
9/30/2016 PRES PRES Treatment Often presents with confusion, agitation. May have concurrent: • Removal of offending agent • Seizure : Tonic Clonic • Reduction of offending agent • Headache : constant, not localized, not relieved with analgesics. • Substitute other CI with caution • Visual disturbances: neglect, aura, hallucinations Physical Exam: • Seizures • Papilledema may be present – Levetiracetam • Deep tendon reflexes are brisk • Babinski sign present – Topiramate • May have incoordination of the limbs. • Hypertension: – Lower diastolic blood pressure in 2-6 hours to <100 mm Diagnosis: Hg, but not > 25% of presenting value • MRI: hyperintense signal on fluid –attenuated inversion recovery image – Labetolol is often first line Differential Diagnosis: PTLD, PML • Can progress to cerebral edema or hemorrhage and death. (Neil, 2015) (Neil, 2015) Infection Infection Treatment Infections can result in altered mental status both inside and outside of the CNS. May • Prophylaxis presented with confusion, agitation, headache or weakness – CMV: Valganciclovir 900 mg PO BID for 3 or 6 months • Maybe fungal, viral or bacteria. based on recipient donor risk factors • Exposure may be donor-related, recipient-related, nosocomial or community – PCP: Trimethoprim/sulfamethoxazole (TMP/SMX) • Viral: three times weekly for one year – Herpes Simplex Virus (HSV) – Cytomegalovirus Virus (CMV) – Fungal: Fluconazole 100 mg once per week for 6 – Varicella zoster virus (VZV) weeks – Epstein–Barr virus (EBV) – Human herpes virus 6 (HHV-6) • Treatment • Fungal – Based on sensitivities – Aspergillosis – Candida – Often in collaboration with transplant ID – Cryptococcus • Bacterial (Zivkovic, 2013) 6
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