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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

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DaZed and COnFuseD

Altered Mental Status Before and After Liver Transplant

Kerry A. Decker, RN, MSN, ANP-BC September 30, 2016

Altered Mental Status

  • Change in level of consciousness
  • Change in the level of awareness and the

ability to focus, sustain, or shift attention

  • Memory difficulties, disorientation, or speech

that is tangential, disorganized, or incoherent

(Francis & Young, 2014)

Altered Mental Status

  • Infectious
  • Metabolic
  • Organ Failure
  • Neurologic Disorders
  • Psychiatric
  • Iatrogenic

(Francis & Young, 2014)

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Altered Mental Status in Liver Patients

  • Infectious

– Bacteremia/ Fungemia – Sepsis

  • Metabolic

– Electrolyte – Glycemic – Nutritional

  • Organ Failure

– Kidney failure: uremia – Liver failure: encephalopathy – Respiratory failure: Hypercarbia/ Hypoxemia

  • Iatrogenic

– Medication – Different environment – Irregular sleep patterns

Causes of Altered Mental Status in Patients with Cirrhosis

Hepatic Encephaphy Infection Metabolic Disorders Drugs Structural Lesions Psychiatric Disorders Other

(Rahimi, Elliott & Rockey, 2013)

Altered Mental Status in Liver Patients Hepatic Encephalopathy

Hepatic Encephalopathy Precipitants in Patients with Cirrhosis Drugs Vascular Occlusion

  • Benzodiazepines
  • Narcotics
  • Alcohol
  • Hepatic vein thrombosis
  • Portal vein thrombosis

Increased ammonia production or absorption Portosystemic Shunting

  • GI Bleed
  • Infection
  • Metabolic Alkalosis
  • Placed shunts
  • Spontaneous shunts

Dehydration Primary HCC

  • Vomiting
  • Diarrhea
  • Hemorrhage
  • Diuretics

(Ferenci, 2016)

Hepatic Encephalopathy:

Diagnosis

  • History
  • Physical Exam:

– Orientation – Asterixis – Hyperreflexia

  • Cultures
  • Labs: AMMONIA level not helpful
  • Abdominal u/s with doppler
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Hepatic Encephalopathy

Stage Description Neuropyschiatric Symptoms Neurological Symptoms Minimal No evidence of LOC Measurable with psychometric testing No physical exam findings Grade I Slight mental slowing Irritability; euphoria; Decreased attention span; altered sleep pattern Fine motor skill impairment Grade 2 Fatigue; apathy Slight disorientation to time Flapping Tremor, Slurred speech Grade 3 Somnolence; confusion Marked disorientation to time and space Clonus, asterixis Grade 4 Coma

  • Unresponsive to

painful stimuli Covert Overt

(Vilstru, Amodio, & Bajaj, 2014; Zhan & Stremmel, 2012)

Hepatic Encephalopathy:

Treatment

  • Identifying the underlying cause

– Diagnose and treat infection – Stop GI bleed – Correct electrolyte imbalance – Stop narcotics and sedatives – Identify cancer or vascular occlusion

  • 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

– Polyethylene glycol

  • Small study of 50 patients randomized to either lactulose or

polyethylene glycol demonstrated resolution of HE sx.

(Rahimi, Singal, Cuthbert & Rockey, 2014) (Vilstrup, Amodio, Bajaj, & Cordoba, 2014)

Hepatic Encephalopathy:

Treatment

Post Transplant

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Altered Mental Status

  • Infectious

– Bacteremia – Fungemia

  • Metabolic

– Primary nonfunction – Small for size

  • Iatrogenic

– Medication

  • Steroids
  • Calcineurin Inhibitors

Small for Size Syndrome

Defined

Clinical syndrome defined by the presence of prolonged cholestasis, coagulopathy and ascites,

  • ccurring when a partial liver graft is inadequate to

sustain metabolic demand in the recipient. Increased portal inflow leads to hepatic congestion

(Alejandoro- Hernandez, 2016)

Small for Size Syndrome

Criteria

Size and flow:

  • Graft weight to recipient body weight ratio <0.8 &

PVF>250 ml/min/100g Two out of Four: – Ascites

  • >1000 Ml on 3 consecutive days post op week 1 or on day 14
  • >500 ml on POD day 28

– Hyperbilirubinemia

  • >5 on 3 consecutive days post op week 1 or on day 14

– Prolonged PT/INR

  • Uncorrected INR >2 on 3 consecutive days post op week 1

– Altered MS

  • Grade 3/4 hepatic encephalopathy

No other cause for the above

(Alejandoro- Hernandez, 2016)

Small for Size Syndrome

Treatment

  • Decreasing portal inflow

– Medically

  • Octreotide 50-100 mcg/hr x 5 days

– Surgically

  • Shunt operation: mesocavl shunt, portocaval shunt and

splenorenal shunt

  • Splenectomy
  • Increase hepatic vein outflow

– Surgically

  • Include middle hepatic vein in right lobe grafts
  • Hepatic Encephalopathy Tx
  • Liver Growth

(Alejandoro- Hernandez, 2016)

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Steroid Psychosis

Steroid psychosis may manifest as depression, mania, psychosis and delirium

  • Incidence is about 22% for neuropsychiatric events
  • 2 fold risk of depression
  • 4-5 x risk of developing mania
  • 4-5 x risk of developing confusion
  • Increased risk with underlying psychiatric disorder
  • Psychotic symptoms are dose dependent.
  • Symptoms have been noted to develop in as little as 40 mg /day, but become

much more common at 80 mg/day

  • Diagnosis is largely based on history of exposure.

(Fardet, Petersen, Nazareth, 2012) (Boston Collaborative Drug Surveillance Program, 1972)

Steroid Psychosis

Treatment

Post-Op Steroid Dose 0 (INTRA-OP) 1000 mg IV x 1 0 (INTRA-OP) 500 mg IV x 1 POD 1 200 mg IV x 1 POD 2 160 mg IV x 1 POD 3 120 mg IV x 1 POD 4 80 mg IV x 1 POD 5 40 mg PO x 1 POD 6 20 mg x 7 days POD 7-13 15 mg PO x 7 days POD 14-20 12.5 mg PO x 7 days POD 14-20 10 mg PO x 7 days POD 21-27 7.5 mg PO x 7 days Thereafter 5 mg PO

  • Steroid reduction
  • Mood stabilizers and

antipsychotic

  • Lithium
  • Olanzapine
  • Haloperidol
  • SSRI
  • Fluoxetine

(Brown & Chandler, 2011; Corbett, Nordstrom, Vilke, Wilson, 2016)

Calcineurin Inhibitor Toxicity

May manifest as headache, tremor, neuralgia, neuropathy, hallucinations, ataxia or seizures.

  • Incidence for neurological event

– 10-28% with cyclosporine – 21-32% with tacrolimus – 18% either

  • Recipients of liver transplant more affected than other transplant patients
  • Predisposing factors may include:

– Hepatic encephalopathy pre transplant – High MELD going into transplant – Lower hgb preoperatively – Acute decompensation of chronic liver disease – Multiple surgeries

  • Not related to dose

(Balderramo, Prieto, Cardenas, Navasa, 2011;

Bechstein, 2000)

  • Acute alteration:

– Removal of offending agent – Try another CI – see steroid psychosis

  • Seizures:

– Phenytoin – Levetiracetam

  • Headaches/Tremors:
  • Propanolol

(Bechstein, 2000)

Calcineurin Inhibitor Toxicity

Treatment

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PRES

Often presents with confusion, agitation. May have concurrent:

  • Seizure: Tonic Clonic
  • Headache: constant, not localized, not relieved with analgesics.
  • Visual disturbances: neglect, aura, hallucinations

Physical Exam:

  • Papilledema may be present
  • Deep tendon reflexes are brisk
  • Babinski sign present
  • May have incoordination of the limbs.

Diagnosis:

  • MRI: hyperintense signal on fluid –attenuated inversion recovery image

Differential Diagnosis: PTLD, PML

  • Can progress to cerebral edema or hemorrhage and death.

(Neil, 2015)

PRES

Treatment

  • Removal of offending agent
  • Reduction of offending agent
  • Substitute other CI with caution
  • Seizures

– Levetiracetam – Topiramate

  • Hypertension:

– Lower diastolic blood pressure in 2-6 hours to <100 mm Hg, but not > 25% of presenting value – Labetolol is often first line

(Neil, 2015)

Infection

Infections can result in altered mental status both inside and outside of the CNS. May presented with confusion, agitation, headache or weakness

  • Maybe fungal, viral or bacteria.
  • Exposure may be donor-related, recipient-related, nosocomial or community
  • Viral:

– Herpes Simplex Virus (HSV) – Cytomegalovirus Virus (CMV) – Varicella zoster virus (VZV) – Epstein–Barr virus (EBV) – Human herpes virus 6 (HHV-6)

  • Fungal

– Aspergillosis – Candida – Cryptococcus

  • Bacterial

(Zivkovic, 2013)

Infection Treatment

  • Prophylaxis

– CMV: Valganciclovir 900 mg PO BID for 3 or 6 months based on recipient donor risk factors – PCP: Trimethoprim/sulfamethoxazole (TMP/SMX) three times weekly for one year – Fungal: Fluconazole 100 mg once per week for 6 weeks

  • Treatment

– Based on sensitivities – Often in collaboration with transplant ID

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Dazed and Confused

  • Take mental status changes seriously
  • Subtle differences can be the beginning of

something more serious

  • Collaboration with the multidisciplinary

healthcare team and patient’s support system is helpful for identification and treatment

References

Alejnadro-Hernandez, R. (2016) Small for size syndrome in liver transplantion-new horizons to cover with a good launch-pad. Liver Transplantation. Accepted article. doi: 10.1002/lt.24513 Balderramo, D., Prieto, J. Cardenas, A, Navasa, M. (2011) Hepatic encephalopathy and post-transplant hyponatremia predict early calcineurin inhibitor-induced neurotoxicity after liver transplantation. Transplant International, 24 (8): 812-819. doi: 10.1111/j.1432-2277.2011.01280.x. Bechstein, W.O. (2000) Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transplant International, 13: 313-326. doi:10.1111/j.1432-2277.2000.tb01004.x Bernhardt, M., Pflugrad, H., Goldbecker, A., Barg-Hock, H, Knitsch, W., Klempnauer, J., Strassburg, C.P, Hecker, H., et al. (2015) Central nervous system complications after liver transplantation: Common but mostly transient phenomena. Liver Transplantation, 21, (2): 224-231. doi: 10.1002/lt.24035 The Boston Collaborative Drug Surveillance Program (1972) Acute adverse reactions to prednisone in relation to dosage [Abstract]. Clinical Pharmacology & Therapeutics, 13 (5):694–698. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/5053810 Brown, E. S., & Chandler, P. A. (2001). Mood and cognitive changes during systemic corticosteroid

  • therapy. Primary Care Companion to the Journal of Clinical Psychiatry, 3(1): 17-21. Retrieved from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181154 Chen, S., Hu, J., Xu, L., Brandon, D. & Yu, J. (2015) Posterior reversible encephlopathy syndromea fter transplantion: a review. Molecular Neurobiology. doi:10.1007/s12035-015-9560-0 Corbett, B., Nordstrom, K. Vilke, G.M. & Wilson, M. (2016) Psychiatric emergencies for clinicians: emergency department diagnosis and management of steroid psychosis. The Journal of Emergency

  • Medicine. Accepted article. doi: 10.1016/j.jemermed.2016.05.055

Fardet, L., Petersen, I. & Nazareth, I. (2012). Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. American Journal of Psychiatry, 169 (5): 491-497. Ferenci, P.F. (2016). Hepatic encephalopathy in adults: clinical manifestations and diagnosis. In Travis, A.C. (Ed), UpToDate. Waltham, MA: UpToDate: Retrieved from www.uptodate.com Francis, J. & Young, G.B. (2016) Diagnosis of delirium and confusional states. In Wilterdink, J.L. (Ed),

  • UpToDate. Waltham, MA: UpToDate: Retrieved from www.uptodate.com

Graham, J. A., Samstein, B., & Emond, J. C. (2014). Early Graft Dysfunction in Living Donor Liver Transplantation and the Small for Size Syndrome. Current Transplantation Reports, 1(1), 43–52. http://doi.org/10.1007/s40472-013-0006-1 Neill, T. A. (2015). Reversible posterior leukoencephalopathy syndrome. In Wilterdink, J.L. (Ed) ,

  • UpToDate. Waltham, MA: UpToDate: Retrieved from www.uptodate.com

Rahami, R., Singal, A. G, & Rockey, D.C. (2014) Lactulose vs polyethylene glycol 3350-electrolyte solultion for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Internal Medicine, 174 (11): 1727 -1733. doi: 10.1001/jamainternmed.2014.4746. Rahami, R., Elliott, A.C, & Rockey, D.C. (2013) Altered mental status in cirrhosis: etiologies and

  • utcomes. Journal of Investigative Medicine, 61 (4), 695-700. doi:

10.2310/JIM.0b013e318289e254 Vilstrup, H., Amodio, P. , Bajaj, J., Cordoba, J., Ferenci, P., Mullen, K.D et al. (2014) Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology, 60 (2):715- 535. doi: 10.1002/hep.27210. Zivkovic, S.A. (2013) Neurologic complications after liver transplantation. World Journal of Hepatology, 5 (8), 409-416. http://doi.org/10.4254/wjh.v5.i8.409 Zhan, T. & Stremmel, W. (2012) The diagnosis and treatment of minimal hepatic encephalopathy. Deutsches Ärzteblatt international, 109 (10), 180-7. doi: 10.3238/arztebl.2012.0180