CDAD in Neurocritical Care Unit (Data Collection)

Incidence of CDAD:

  1. general ICU setting – rates between 1 and 13%
  2. in Neurocritical Care Unit = 0.6% [1] or 0.4% [2]

DEFINITION: adult patient developing diarrhea with (+) EIA >48h after admission to neurocritical care unit


Clinical Data:

  • Age
  • Gender
  • Admit date to unit
  • Diagnosis on admission
  • APACHE II scores
  • Date of CDAD diagnosis

Method of Diagnosis:

  • Stool cytotoxin assay
  • Stool EIA
  • Histology
  • Endoscopy

DISEASE SEVERITY: (UK Health Protection Agency Definition for diarrhea and disease severity)

  • MILD – normal WBC and ❤ type 5-7 stools per day (Bristol stool chart)
  • MODERATE – raised WBC <15 and loose motions (i.e. 3-5 type 5-7 stools/day)
  • SEVERE – WBC >15, T >38.5, acute rise in plasma creatinine (>50% baseline) and clinical/radiological signs of severe colitis
  • LIFE THREATENING – hypotension, partial / complete ileus or toxic megacolon / CT evidence of severe colitis


Risk Factors associated with C. difficile infection:

  • antibiotic use
    • Prophylactic – cephalosporin / etc
    • Treatment – cephalosporin / PCN / MNZ, vancomycin / quinolone / AG / etc
      • Microbiological cultures
      • Other causes of sepsis
  • laxative use
  • nasogastric feeding
  • antisecretory drugs (PPI / antihistamines)
  • steroid use
  • GI stimulants (metoclopramide / erthromycin)

Risk factors associated with ICU-associated CDAD:

  • advanced age > 65y
  • length of hospital stay
  • colonization pressure (duration of time and number of infectious contacts a susceptible patient is exposed to
  • antibiotic use
  • vancomycin resistant enterococci
  • use of medical devices (mech ventilation, urinary catheters, central lines)


  • None
  • MNZ
  • Vancomycin
  • Both


  • Nonresponse
  • Toxic megacolon


  • ICU outcome
    • Discharge
    • Mortality
  • Hospital outcome 
    • Discharge
    • Mortality


[1] Musa, S., Robertshaw, H., Thomson, S., Cowan, M., & Rahman, T. (2010). Clostridium difficile-Associated Disease Acquired in the Neurocritical Care Unit. Neurocritical Care13(1), 87-92. doi: 10.1007/s12028-010-9374-x

[2] Tripathy, S., Nair, P. and Rothburn, M. (2013). Clostridium difficile Associated Disease in a Neurointensive Care Unit. Frontiers in Neurology, 4.


The DOPAST Trial

DOPAST = Duration of Prophylaxis after SAH Trial. (T. Human / M. Diringer et al, Wash U. St. Louis School of Medicine)

Study Objectives: compare brief versus extended seizure prophylaxis after aSAH.

Study Design: prospective, single-center, randomized, open-label trial

Comparisons: brief (3-day) course of levetiracetam vs extended treatment (until hospital discharge)

Outcomes: in-hospital seizure (primary), drug discontinuation / functional outcome (secondary)


  • 84 patients randomized, trial terminated due to slow enrollment
  • In-hospital seizures: 9% in brief course, 2% in extended group
  • Discontinuation: 20% of extended group
  • Functional outcome: good outcome more likely in brief course (83% vs 61%, p=0.04)

Conclusions: underpowered to demonstrate superiority of extended seizure prophylaxis, though trend to benefit seen

NOTE: seizures primarily occurred in those with radiographic early brain injury (EBI). EBI = radiogrpahic evidence of parenchyma injury on brain imaging performed on the first 5 days of SAH. This includes aneurysm-related ICH, early or procedural infarction, other visible hypodensity (e.g. retraction injury).


    EBI correlation with seizures – possibly longer duration prophylaxis for patients with EBI
    Study inconclusive regarding optimum length of seizure prophylaxis, needs a larger trial


Human, T., Diringer, M., Allen, M., Zipfel, G., Chicoine, M., Dacey, R. and Dhar, R. (2017). A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Wald, A. (2019). Update on the Management of Constipation. JAMA.

The BASICS Trial

B.A.S.I.C.S. = British Antibiotc and Silver Impregnated Catheters for Shunts multicenter RCT.

This multicenter, single-blind RCT looked at the cost-effectiveness of antibiotic-impregnated shunts or silver shunts com are with standard shunts at reducing infection.

Study included 21 regional adult and pediatric neurosurgery centers in the UK and Ireland.

Inclusion Criteria: patients of any age with hydrocephalus of any etiology, requiring a first VPS; patients with failed primary endoscopic third ventriculostomy, previous indwelling EVD and indwelling ventricular access device were included.

Exclusion Criteria: evidence of active and ongoing CSF or peritoneal infection, previous VPS, multilingual Ted HCP requiringmultiple shunts or neuroendoscopy, known allergy to rifampicin, clindamycin or silver, or if VA or VPS was planned.

There are three types of shunt catheters: standard, antibiotic-impregnated (0.15% clindamycin + 0.054% rifampicin) and silver-impregnated.

The following data were collected:

  • Temperature
  • HA
  • Lethargy
  • Meningism
  • Consciousness level
  • Wound erythema
  • Peripheral WBC
  • CRP
  • Microbiological analysis of CSF (microscopy and culture)
  • Type of treatment initiated (ABx prescribed / shunt removal)

Primary Outcome: time to shunt failure due to infection; shunt failure classified as being due to infection or not.

Reasons for shunt failure classified as:

  • Infection
  • Mechanical (blockage of any component s.a. Valve or catheters)
  • Patient-related (unrelated medical condition, e.g. appendicitis)
  • Functional (change of valve for symptomatic overdrainage or underdrainage of CSF, change from fixed-pressure valve to programmable valve)

Infection Definitions for Classification of Shunt Failure

  • DEFINITE (culture-positive)
    • (+) growth CSF on primary culture or repeated subculture (growth identified after enrichment of primary sample by overnight broth incubation and subculture into fresh medium)
    • +/- signs of infection and
    • managed by shunt removal and antibiotic treatment
  • PROBABLE (culture-uncertain)

    • (+) growth CSF on 1 subculture only
    • +/- signs clinical signs of infection with
    • CSF pleocytosis or organisms of GS or both and
    • Managed by shunt removal and antibiotic treatment

    PROBABLE (culture-negative)

    • (-) growth on CSF cultures
    • With CSF pleocytosis or organisms on GS or both
    • +/- clinical signs of infection
    • Managed by shunt removal and antibiotic treatment
    POSSIBLE (culture-uncertain)

    • No signs of infection
    • No CSF pleocytosis
    • No organisms on GS
    • (+) growth on CSF culture after enrichment in 1 CSF sample only
    • Managed by shunt removal and antibiotic treatment
    SHUNT DEEP INCISION INFECTION Infection of deep surgical wound and subcutaneous shunt

    • No evidence of CSF infection
    • Managed by shunt removal and antibiotic treatment

Figure. Cumulative incidence plot of infection by shunt type.


  • 3505 patients assesses
  • 1605 randomized
    • 536 standard shunt group
    • 538 antibiotic shunt group
    • 531 silver shunt group
  • Shunt revisions

    • 398 (25%) had revision operations
    • 75 (5%) classified as shunt infections

    antibiotic shunt decreased the incidence of shunt failure due to infection over time compared to standard shunts; silver shunts were comparable with standard shunts (no difference)

    • 6% of standard, 6% of silver shunts and 2% of antibiotic shunts had an infection

    No significant difference between all 3 shunts for time to shunt failure for any cause (# of shunt failures similar between the 3 groups, but underlying reason differed)

    Patients with all 3 shunt types had similar # of GN infections

TAKE-HOME MESSAGE: The BASICS trial provided sound evidence on the use of antibiotic shunts to reduce infection.


Mallucci, et al. Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation. VOLUME 394, ISSUE 10208, P1530-1539, OCTOBER 26, 2019. Open Access Published:September 12, 2019 DOI:

NIV+HFNO Post-Extubation

A study recently completed in 30 ICUs in France looked at patients at high risk for reintubation and the effects of high-flow nasal oxygenation (HFNO) only versus noninvasive ventilation + HFNO, in preventing reintubation.

Inclusion criteria

  • Age >65y or 
  • Underlying chronic lung diseases COPDobesity-hypoventilation syndromerestrictive pulmonary disease
  • Underlying chronic cardiac disease LV dysfunction, EF <=45%h/o cardiogenic pulmonary edemadocumented IHDpermanent Afib

Exclusion criteria

  • long term treatment with NIV or CPAP at home
  • C/I to NIV
  • underlying neuromuscular disease (myopathy / MG)
  • TBI leading to intubation
  • unplanned extubation
  • DNR/DNRI orders


  • CONTROL GROUP:  HFNO alone x 48hSettings: flow of 50L/min, FiO2 adjusted to obtain SPO2 >=92%, temp of heated humidifier set at 37C
  • INTERVENTION GROUP:  NIV immediately after extubation, first session at least 4h and minimal duration of 12h/day during first 48hContinuous NIV throughout nightSettings: Use ICU ventilator with NIV mode or dedicated bilevel ventilator in PS mode with minimal PS of 5 cm H20, targeting TV 6-8ml/Kg of predicted body weight, PEEP level between 5-10 cm H20 and FiO2 adjusted to SPO2 >=92%HFNO is delivered in between NIV sessions
  • if no signs of respiratory failure, treatment stopped and switched to standard oxygenation


648 patients randomized, 641 patients completed the trial. Reintubation rate at Day 7 was 11.8% with HFNO+NIV and 18.2% with HFNO. Proportion of patients with post-extubation respiratory failure at Day 7 and reintubation rates up until ICU discharge were significantly lower with HFNO+NIV than with HFNO alone. ICU mortality rates not significantly different.


  • extubate to BiPAP, PS 5 cm H20 (goal TV 6-8ml/Kg), PEEP 5-10cm H20
  • adjust FiO2 to keep stats >=92%
  • keep BiPAP as tolerated (minimum 4 hours first session, at least 12 hours per day)
  • may switch to HFNO in between sessions
  • continuous BiPAP at night


Thille, A., Muller, G., Gacouin, A., Coudroy, R., Decavèle, M., Sonneville, R., Beloncle, F., Girault, C., Dangers, L., Lautrette, A., Cabasson, S., Rouzé, A., Vivier, E., Le Meur, A., Ricard, J., Razazi, K., Barberet, G., Lebert, C., Ehrmann, S., Sabatier, C., Bourenne, J., Pradel, G., Bailly, P., Terzi, N., Dellamonica, J., Lacave, G., Danin, P., Nanadoumgar, H., Gibelin, A., Zanre, L., Deye, N., Demoule, A., Maamar, A., Nay, M., Robert, R., Ragot, S. and Frat, J. (2019). Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure. JAMA, 322(15), p.1465.


The BRAIN Score is a 24-point score based on the following components:

  • Baseline ICH volume
  • Recurrent ICH
  • Anticoagulation with warfarin at symptom onset
  • Intraventricular extension
  • Number of hours to baseline CT from symptom onset

This score predicted hematoma expansion with 85.8% probability.

Study based on INTERACT2 data.

  • Larger baseline ICH may reflect multiple bleeding points from arteries or arterioles or under high systemic arterial pressure with further induction of perilesional hemorrhage.
  • The earlier a patient is first scanned, the greater the probability of later demonstrating ICH growth.
  • Patients taking warfarin at the time of ICH experience more prolonged bleeding, which may persist beyond 24h.
  • IVH not only indicates more active hemorrhage, but also more active inflammatory cytokines and altered systemic homeostatic / fibrinolytic pathways, leading to a coagulopathic state.
  • Patients with recurrent ICH are likely to have more severe underlying chronic SVID, predisposing them to larger and more rapid growth in ICH.

How to use this score? Hmmm, not sure how to use at the bedside.

– triage patients for more intensive monitoring or intervention?

*>90% of subjects in this study were Chinese, need to further validate this score in other ethnic populations.


Garg, R., & Biller, J. (2019). Recent advances in spontaneous intracerebral hemorrhage. F1000research, 8, 302. doi: 10.12688/f1000research.16357.1

Wang, X., Arima, H., Al-Shahi Salman, R., Woodward, M., Heeley, E., & Stapf, C. et al. (2015). Clinical Prediction Algorithm (BRAIN) to Determine Risk of Hematoma Growth in Acute Intracerebral Hemorrhage. Stroke, 46(2), 376-381. doi: 10.1161/strokeaha.114.006910

Aspirin use reduces size of Unruptured aneurysms?!

Authors performed a retrospective review of a database looking at the effect of aspirin use in patients with multiple intracranial aneurysms. Statistical analysis showed that ASA use was associated with a decreased rate of growth (OR 0.19, 95% CI 0.05-0.63!!!).

Aspirin was hypothesized to decrease risk of rupture by stabilizing the aneurysm walls and counteracting proinflammatory pathways that play a key role in propagating aneurysm wall weakening.


Zanaty, M., Roa, J., Nakagawa, D., Chalouhi, N., Allan, L., & Al Kasab, S. et al. (2019). Aspirin associated with decreased rate of intracranial aneurysm growth. Journal Of Neurosurgery, 1-8. doi: 10.3171/2019.6.jns191273

The BAT Score – Predicting Hematoma Expansion With A NCCT


BAT score was developed to predict hematoma expansion in spontaneous acute ICH based on a noncontrast CT.


The following CT markers were included:

  1. hypodensities
  2. blend sign
  3. hematoma shape and density
  4. fluid level

*hematoma expansion = growth >6ml or >33%.


The following were noted to predict hematoma expansion and included in the score:

  1. blend sign (odds ratio, 3.09; 95% confidence interval [CI],1.49-6.40; P=0.002)
  2. any intrahematoma hypodensity (odds ratio, 4.54; 95% CI, 2.44-8.43; P<0.0001)
  3. time from onset to NCCT <2.5 hours (odds ratio, 3.73; 95% CI, 1.86-7.51; P=0.0002)

5 point score was created: 1 point for blend sign, 2 points for any hypodensity, 2 points for timing of NCCT <2.5 hours.  A dichotomized bat score (>=3) predicted HE with Sn 0.50 and Sp 0.89.



Morotti, A., Dowlatshahi, D., Boulouis, G., Al-Ajlan, F., Demchuk, A., & Aviv, R. et al. (2018). Predicting Intracerebral Hemorrhage Expansion With Noncontrast Computed Tomography. Stroke49(5), 1163-1169. doi: 10.1161/strokeaha.117.020138

ONSD Technique – Ocular US for Detection of Raised ICP

Ocular ultrasound advantages:

  • Comparable to CT scan for detecting raised intracranial pressure
  • -Point of care
  • Rapid assessment tool
  • Very high sensitivity and specificity for detecting elevated ICP (but doesn’t help identifying cause)
  • Quick learning curve
  • Easily available tool even in field or remote situations

Journal Article: Sonography of the Optic Nerve Sheath Diameter for Detection of Raised Intracranial Pressure Compared tc Computed Tomography A Systematic Review

Sonography of the optic nerve sheath diameter compared to CT performed exceptionally well for diagnosis of raised ICP.

    Sensitivity of 95.6% (95% Cl, 87.7%-98.5%)
    Specificity of 92.3% (95% Cl. 77.9%-98.4%).
    Positive likelihood ratio of 12.5 (95% Cl, 4.2-37.5)
    Negative likelihood ratio of 0.05 (95% Cl 0.016-0.14)
    Prevalence ranged from 13.6% to 100%


Normal ONSD ranges from 4.7-5mm.

OSND cut off value above 5mm detects raised ICP (>20mmHg) with high sensitivty and specificity.

  • Higher values of OSND increases specificity at the compromise of sensitivity
  • Sensitivity and specificity varies with:
  1. Threshold Optic nerve sheath diameter
  1. Prevalence of elevated ICP in the population under study

Ocular sonography shows good diagnostic test accuracy for detecting raised ICP compared to CT:

  • High sensitivity for ruling out raised ICP in a lowrisk group.
  • High specificity for ruling in raised ICP in a highrisk group.

Scanning Technique

  • Linear 6-13 Mh-lz probe
  • Depth settings ~4cms
  • Apply transparent adhesive film to eye
  • Use Copious Gel
  • Scan in Longitudinal and Transverse axis

Sono Anatomy

Key aspects of scanning technique:

  • Scan in both sagittal and transverse axis
  • Ensure lens or iris is in the scan else you are scanning nerve off-axis.
  • Off-axis, may underestimate OSND diameter.
  • Good view of the nerve often necessitates moving the probe slightly to the temporal side and angulating the beam a little nasally.
  • Once good view obtained, freeze image
  • ONSD measurement is made 3mm below the retinal surface
  • Measure Outside Diameter (OD) of optic nerves

Papilledema on US:

  • ONSD measurement with ultrasonography has a reproducibility with a median intraobserver reliability of 0.2mm (range 0.1-0.5 mm)
  • The learning curve is quick – an estimated 10 scans for the experienced sonoarapher and 25 for the novice with abnormal scans (Tayal et al, Annals of Emerg Med 2007)

Key pitfalls:

Measurement of ONSD is a qualitative rather than quantitative assessment of ICP. (As changes in ONSD and ICP dont have a linear relationship).


Ocular sonography shows good diagnostic test accuracy for detecting raised ICP compared to CT

In a general population with low prevalence of raised ICP, the ONSD is excellent for RULING OUT the diagnosis of raised ICP (Negative predictive value).

In a population with a high clinical suspicion (e.g. Trauma with reduced GCS), the optic nen/e sheath diameter is excellent at RULING IN the diagnosis of raised ICP (Positive predictive value)

This noninvasive point-of-care method could lead to:

  1. In unconscious patient rule out raised ICP as a cause
  1. With early detection, Rapid interventions for raised ICP
  1. Assess centers tight out CT to triage patients for referral
  1. Monitor patients during transport
  1. As part of a protocol to reduce CT use (in population with low prevalence.)
  2. Prior to lumbar puncture to rule our raised ICP noninvasively


Information gathered from YouTube lecture: