Monthly Archives: July 2016

SETScore for Early Tracheostomy in Stroke


**APS acute physiology score, LIS lung injury score


  • initially an in-house screening tool for tracheostomy prediction
  • performed within 1st 24 hours after admission – use worst value in the first 24 hours
  • Dysphagia either
    • reported from a transferring neurological department or
    • observed by clinical signs on admission
      • non-successful swallowing test
      • impaired saliva handling
      • loss/reduction of gag reflex
    • if already intubated on admission, scored with “0”
  • (Neuro)surgical intervention
    • decompressive surgery, hematoma removal, non-cranial major surgery
    • NOTE EVD or probe placement, thrombectomy, angioplasty for vasospasm or coiling
  • Diffuse lesion = a multilocular or widespread affection of brain (i.e. SAH, brain edema, multiple infarcts, hematomas)
  • hydrocephalus = distension of ventricles requiring EVD
  • total sum ranges between 3 and 37

Previously used (with score of >10) to screen for eligibility to be included in pilot trial of SETPOINT study for early tracheostomy (within 3 days) to standard regimen (late tracheostomy between day7 and day14).




Schönenberger, Silvia et al. “The Setscore To Predict Tracheostomy Need In Cerebrovascular Neurocritical Care Patients”. Neurocritical Care 25.1 (2016): 94-104.



Organ Donor Protocol

VS parameters:

  • SBP >100mm Hg and/or MAP >70mm Hg
  • HR 60-140 bpm
  • Temp 36-38 Celcius

Electrolytes parameters:

  • pH 7.35-7.45    PCO2 35-45    PO2 >100
  • Bicarb 24-30    BE 00 +/- 2
  • Na+ 135-145 mg/dL
  • K+ 3.5-4.5 mg/dL
  • Ca++ >8.7 mg/dL
  • Mg++ >1.5 mg/dL
  • Phosphate >2.5 mg/dL
  • Glucose <200 mg/dL


    • >5.0 (or if UO <1 ml/kg/hr) eliminate KCl from IV fluids
    • 3.7-3.9 mg/dL – 1 run of KCl 10 mEq (premixed)
    • 3.5-3.7 mg/dL – 2 runs of KCl 10 mEq (premixed)
    • 3.3-3.5 mg/dL  – 3 runs of KCl 10 mEq (premixed)
    • 3.1-3.3 mg/dL  – 4 runs of KCl 10 mEq (premixed)
    • <3.1mg/dL         –  contact coordinator
  • GLUCOSE – check serum glucose q4h
    • >500 mg/dL 20 units Regular insulin IV
    • >400 mg/dL 15 units Regular insulin IV
    • >300 mg/dL 10 units Regular insulin IV
    • >200 mg/dL 5 units Regular insulin IV
    • >100 mg/dL 3 units Regular insulin IV
    • >160 Run D5W for primary IV
    • >150 Run D5W/0.2NS for primary IV
    • 135-150 Run 0.45NS for primary IV
    • <135 Run NS for primary IV
    • <8.7 (if ionized Ca <4.2) Calcium chloride 1 Gm IV over 10 minutes
    • <1.5 Magnesium sulfate 10% 1.5 ml/min infusion
    • <2.5 Potassium phosphate replacement (no specific dose indicated)


    • Dopamine infusion:  400mg in D5W 250ml premixed, titrate to SBP >100
    • Dobutamine infusion (if hypotensive from cardiac dysfunction):  250mg in D5W 250ml premixed, titrate to SBP >100
    • Norepinephrine infusion:  8mg in D5W 500ml, titrate to SBP >100
  • LEVOTHYROXINE protocol (if prescribed by transplant coordinator)
    • Monitor glucose and potassium levels q2h.
    • administer IV bolus of in rapid succession:
      • dextrose 50% x 1 amp (50 ml)
      • solumedrol 1 gram
      • regular insulin 20 units
      • levothyroxine 20 mcg
    • Begin Levothyroxine infusion (200 mcg in 500 ml NS) at 25 ml/hr
    • Reduce pressors as much as possible and adjust levothyroxine infusion to maintain SBP >100
    • if UO >400cc/hr x 2 hours – 5 units aqueous vasopressin (Pitressin) ffd by infusion: Vasopressin 50 units in D5W 500mL at 20 ml/hr
    • titrate to urine output 100-150cc/hr
    • bolus 5 units vasopressin q2h PRN if IV pump not available



New York Organ Donor Network’s “ICU Donor Guidelines and Routine Orders”

Antibiotic-Associated Encephalopathy

What are the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE)?

3 types of AAE

  1. Type 1 AAE
    • onset within days of antibiotic initiation
    • common occurrence of myoclonus or seizures, abnormal EEG, normal MRI, and resolution within days
    • seen with penicillin and cephalosporins
    • most common in setting of renal insufficiency.
  2. Type 2 AAE
    • onset within days of antibiotic initiation
    • frequent occurrence of psychosis, rare seizures, infrequently abnormal EEG (nonspecific rather than epileptic), normal MRI, and resolution within days
    • seen with procaine penicillin, sulfonamides, fluoroquinolones, and macrolides
  3. Type 3 AAE
    • seen only with metronidazole
    • onset weeks after initiation
    • frequent occurrence of cerebellar dysfunction, rare seizures, rare and nonspecific EEG abnormalities, and omnipresence of abnormal MRI
  4. Isoniazid did not fit into any of these categories
    • time to onset is weeks to months
    • psychosis is common, seizures are rare, EEG is frequently abnormal but nonspecifically



*INH does not fit into any of the subtypes.



  • Time of onset after antibiotic initiation – 5 days (except INH and MNZ – 3 weeks)
  • Time to resolution of encephalopathy after ABx discontinuation – 5 days (except MNZ – 13 days)
  • MRI findings
    • abnormal in all MNZ-associated encephalopathy but normal in all others
      • T2 hyperintensities in dentate nuclei of cerebellum (also ?involvement of brainstem, corpus callosum, etc)
    • Bilateral frontal subcortical T2 MRI hyperintensities in isolated case of cefditoren pivoxil toxicity
  • CT findings
    • normal in all cases except 1 case of cerebellar hypodensity with MNZ toxicity and 1 report of L thalamic hypodensity with imipenem toxicity
  • EEG findings:
    • abnormal in 70%
    • abnormal in nearly all cases of cephalosporin-associated encephalopathy
    • common with PCN (83%), cipro (83%) and INH (69%)
    • most common abnormalities: nonspecific signs of encephalopathy (slowing, generalized periodic discharges with triphasic morphology
    • epileptiform discharges / seizures seen in 28% (55% in cephalosporins, 44% in quinolones and 40% of PCN, but not in macrolides, MNZ or sulfonamides)
  • check serum and CSF trough levels of antibiotics?
    • cefepime trough 0.2 to 1.1 mg/L
    • 50% probability of neurologic toxicity at trough of 22mg/L
    • CSF level during toxicity in 2 cases with values of 2.4 mg/L and 18 mg/L

A – FLAIR hyperintensities bilatearl deep cerebellar nuclei
B – DWI showing restricted diffusion in splenium with MNZ toxicity
C – ADC sequences






Bhattacharyya, Shamik et al. “Antibiotic-Associated Encephalopathy”. Neurology 86.10 (2016): 963-971.

Eloquent Areas in AVM Surgery




AEDs in Renal Failure / Hemodialysis


How does renal disease affect AED levels?

  • Renal insufficiency alters the pharmacokinetics of seizure medications that are metabolized by the kidneyes, leading to increased half-lives and accumulation of the drug.
  • Albuminuria and acidosis that frequently occur in renal failure also decreases drug binding, increasing the free levels of AEDs and volume of distribution.
  • Gastroparesis delays maximum serum levels of AEDs, intestinal edema diminishes absorption of AEDs.

Take home message:  It is difficult to predict drug levels based on the creatinine clearance.

AEDs that are extensively eliminated by kidneys:

  • hydrosoluble
  • low molecular weight
  • low Vd
  • little protein-bound
  • Examples:  gapabentin, topiramate, ethosuxamide, vigabatrin, levetiracetam
  • accumulate in renal disease
  • easily removed by hemodialysis and requires post-HD administration

AEDs that are not extensively eliminated by kidneys:

  • lipophylic
  • high protein-bound
  • Examples:  carbamazepine, phenytoin, lamotrigine, benzodiazepines, valproate
  • little affected by renal disease
  • HD has little impact on carbamazepine, phenytoin and valproate levels
  • HD has unpredictable effects on benzodiazepines or oxcarbazepine monohidroxi derivative
  • 4-hour HD decreases lamotrigine levels by ~20%

Peritoneal dialysis has variable effects on AED serum levels, check free levels for drug adjustment


  • CrCl >80 mL/minute/1.73 m2: 500 to 1,500 mg every 12 hours
  • CrCl 50 to 80 mL/minute/1.73 m2: 500 to 1,000 mg every 12 hours
  • CrCl 30 to 50 mL/minute/1.73 m2: 250 to 750 mg every 12 hours
  • CrCl <30 mL/minute/1.73 m2: 250 to 500 mg every 12 hours
  • End-stage renal disease (ESRD) requiring hemodialysis: Dialyzable (50%); 500 to 1,000 mg every 24 hours; supplemental dose of 250 to 500 mg is recommended posthemodialysis
  • Peritoneal dialysis (PD): 500 to 1,000 mg every 24 hours (Aronoff 2007)
  • Continuous renal replacement therapy (CRRT): 250 to 750 mg every 12 hours (Aronoff 2007)


  • There are no dosage adjustments provided in the manufacturer’s labeling; <5% excreted as unchanged drug. Serum concentration may be difficult to interpret in renal failure. Monitoring of free (unbound) concentrations or adjustment to allow interpretation is recommended.
  • Fosphenytoin:  There are no dosage adjustments provided in the manufacturer’s labeling. Free (unbound) phenytoin levels should be monitored closely in patients with renal disease or in those with hypoalbuminemia; furthermore, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance in these patients leading to increase frequency and severity of adverse events.


  • Dosage adjustments are not required or recommended in the manufacturer’s labeling; however, the following guidelines have been used by some clinicians:
  • Children and Adults:
    • GFR <10 mL/minute: Administer 75% of dose
    • Hemodialysis, peritoneal dialysis: Administer 75% of dose (postdialysis)
  • Continuous renal replacement therapy (CRRT):
    • Adults: No dosage adjustment recommended
    • Children: Administer 75% of dose


  • There are no specific dosage adjustments provided in the manufacturer’s labeling; reduced doses are recommended.
  • The following guidelines have been used by some clinicians:
    • CrCl ≥10 mL/minute: No dosage adjustment necessary.
    • CrCl <10 mL/minute: Administer every 12 to 16 hours.
    • HD (moderately dialyzable [20% to 50%]): Administer dose before dialysis and 50% of dose after dialysis.
    • PD:  Administer 50% of normal dose.
    • CRRT: Administer normal dose and monitor levels.


  • Mild to severe impairment: No dosage adjustment necessary (including patients on hemodialysis); however, due to decreased protein binding in renal impairment, monitoring only total valproate concentrations may be misleading.



  • Dosing: Renal Impairment
  • Oral: No dosage adjustment necessary
  • IM, IV: Risk of propylene glycol toxicity. Monitor closely if using for prolonged periods of time or at high doses.
    • Mild-to-moderate disease: Use with caution.
    • Severe disease or failure: Use is not recommended.


  • Dosing: Renal Impairment
    • There are no dosage adjustments provided in manufacturer’s labeling; however, patients with renal failure receiving a continuous infusion cannot adequately eliminate the active hydroxylated metabolites (eg, 1-hydroxymidazolam) contributing to prolonged sedation sometimes for days after discontinuation
  • Intermittent HD:  Supplemental dose not necessary
  • CVVH: Unconjugated 1-hydroxymidazolam not effectively removed; 1-hydroxymidazolamglucuronide effectively removed; sieving coefficient = 0.45
  • PD: Significant drug removal unlikely


  • There are no dosage adjustments provided in the manufacturer’s labeling. Decreased maintenance dosage may be effective in patients with significant renal impairment; has not been adequately studied; use with caution.


  • No dosage adjustment necessary.



Lacerda, Glenda Corrêa Borges de. “Treating Seizures In Renal And Hepatic Failure”. J. epilepsy clin. neurophysiol. 14 (2008): 46-50.

Uptodate.  Accessed 07/12/2016.


Watershed Infarcts

Patients presenting with severe hypertension are at risk for watershed infarcts if blood pressure is rapidly and dramatically reduced, even without frank hypotension.  Blood pressure should be lowered by no more than 25% to reduce the chance of cerebral, coronary or renal ischemia.

Watershed infarcts comprise ~10% of all ischemic strokes.  These infarcts are localized to borderzones between major vascular territories in the brain, and are classified as internal borderzone (IBZ) or cortical borderzone (CBZ) infarcts.


*CBZ in red, IBZ in blue.

The CBZ are located at the junctions of the distal branches of the ACA, MCA and PCA territories.  CBZ infarcts are associated with small cortical infarcts that are more likely due to thromoembolism.

The IBZ are located at the junctions of the distal branches of the ACA/MCA/PCA with the deep perforating arteries (lenticulostriate, artery of Heubner, anterior choroidal artery).  IBZ infarcts are more often associated with severe stenosis or occlusion in the ICA or MCA.  The IBZ is more vulnerable to decreased perfusion due to the anatomic characteristics of cerebral arterioles within this area – being the most distal branches of the ICA, perfusion pressure is likely to be the lowest.  Also the lenticulostriate arteries have limited collateral blood supply.



Patient admitted for hypertensive emergency, started on nicardipine drip and blood pressure lowered from 200+ to 100 systolic.  Relative hypotension maintained for 2 hours.  Patient became comatose thereafter.  MRI showed IBZ infarcts.


Patient with aortic dissection, BP lowered from 200s with nicardipine drip.  Patient became unarousable at SBP 114 where it remained for ~3 hours.   MRI showed IBZ and corpus callosum infarctions.  Patient never regained consciousness.




Kurowski, Donna, Michael T. Mullen, and Steven R. Messé. “Pearls & Oy-Sters: Iatrogenic Relative Hypotension Leading To Diffuse Internal Borderzone Infarctions And Coma”. Neurology 86.24 (2016): e245-e247.

Classification of Hemorrhagic Transformation

Hemorrhagic infarction (HI) describes a heterogeneous hyperdensity in in an ischemic infarct zone.  Parenchymatous hematoma (PH) refers to a more homogenous, dense hematoma with mass effect.  Fiorelli, et al in 1999 refined these definitions to include two subtypes of HI and two subtypes of PH.

Definitions as per Fiorelli (1999):

  • HI is a petechial infarction without space-occupying effect.
  • PH is a hemorrhage (coagulum) with mass effect.
  • 2 subtypes of HI:
    • HI1 (small petechiae)
    • HI2 (more confluent petechiae)
  • 2 subtypes of PH:
    • PH1 (≤30% of the infarcted area with some mild space-occupying effect)
    • PH2 (>30% of the infarcted area with significant space-occupying effect, or clot remote from infarcted area)


Hemorrhages that occur within the first week after stroke were more likely to be PH2-type, whereas hemorrhages that occur later tend to be HI1, HI2 or PH1.  PH2-type was found to be a significant predictor of neurologic deterioration (OR32.3) and of 3 month mortality (OR 18.0) whereas HI1, HI2 and PH1 were not associated with either increased morbidity or mortality.



Subtypes of hemorrhagic transformation: HI1 (top left), HI2 (top right), PH1 (bottom left), and PH2 (bottom right).



Fiorelli, M. et al. “Hemorrhagic Transformation Within 36 Hours Of A Cerebral Infarct : Relationships With Early Clinical Deterioration And 3-Month Outcome In The European Cooperative Acute Stroke Study I (ECASS I) Cohort”. Stroke 30.11 (1999): 2280-2284.

Sussman, Eric S. and E. Sander Connolly. “Hemorrhagic Transformation: A Review Of The Rate Of Hemorrhage In The Major Clinical Trials Of Acute Ischemic Stroke”. Frontiers in Neurology 4 (2013): n. pag.