The Effect of Lumbar Cerebrospinal Fluid Drainage on the Neurologic Outcome Improvement in Out of Hospital Cardiac Arrest Patients Underwent Targeted Temperature Management
Conditions: Heart Arrest, Out-Of-Hospital, Brain Swelling
Sponsor: Chungnam National University Hospital

NCT number: not yet assigned 
 
25 October 2019 
The Effect of Lumbar CSF drainage on the Neurologic Outcome Improvement 
in OHCA underwent TTM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCT number: not yet assigned 
 
25 October 2019 
 
1. Introduction 
Global cerebral ischaemic-reperfusion brain injury following cardiac arrest (CA) can lead to intracranial 
hypertension and, occasionally, acute brain swelling [1,2]. Even small increases in brain volume due to 
oedema can result in harmful increases in intracranial pressure due to the brain’s rigid encasement. The 
previous studies demonstrated a higher intracranial pressure (ICP) was strongly associated with and 
seemed predictive of a poor outcome, and higher ICP following global cerebral ischaemia immediately 
after ROSC, and severe blood-brain barrier (BBB) disruption began at 24 h after ROSC in the poor 
neurologic outcome group treated with target temperature management (TTM) [3, 4]. 
Several therapeutic approaches have been established for the treatment of increased ICP in traumatic 
brain injury, including TTM, elevation of the head, sedation, volume resuscitation, maintenance of 
adequate arterial oxygenation, cerebrospinal fluid drainage via a ventriculostomy, moderate 
hyperventilation, and mannitol administration [5]. However, despite these various therapies, a 
considerable number of patients remain nonresponsive to aggressive management strategies. During the 
last decades, controlled lumbar cerebrospinal fluid (CSF) drainage has been considered to be 
contraindicated in the setting of increased ICP because of the possibility of transtentorial or tonsillar 
herniation [6–8]. In contrast, a recent report on the use of lumbar CSF drainage to treat refractory 
increased ICP suggested that this controversial therapeutic strategy might be efficient and a valuable 
treatment when applied to carefully selected patients had discernible basal cisterns and controlled 
release of CSF under monitoring of ICP and vital signs [9, 10]. Plus, much of the CSF volume is present 
in the subarachnoid spaces and cisterns around the brain. This CSF is not accessible for drainage by 
ventriculostomies but is accessible by lumbar drainage [11]. 
However, to the best of our knowledge, there is no study on the effect of lumbar CSF drainage to 
improve neurologic outcome in CA patients treated with TTM. We aimed to evaluate the effect of 
lumbar CSF drainage on neurologic outcome in post-CA patients treated with TTM. 
 

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25 October 2019 
2. Methods 
This study was approved by the Institutional Review Board of the Chungnam National University 
Medical Centre (CNUH IRB 2019-07-033-003). We obtained approval and consent from the next of 
kin before enrolment. 
2.1. Study design and patients 
This was a prospective single-centre study conducted from November 2019 to October 2021 on patients 
who had been treated with TTM following CA. The primary endpoint was to evaluate the effect of the 
lumbar CSF drainage on attenuation of brain swelling and improvement of the neurologic outcome in 
post-CA patients treated with TTM. The data were collected from the electrical medical record. We 
named the patients were treated with our standard protocol as the non-lumbar CSF drainage group, 
whereas the patients treated with the protocol and the lumbar CSF drainage were called as the lumbar 
CSF drainage group. The neurologic status of the patients was obtained on the 6-month follow-up after 
return of spontaneous circulation (ROSC). Neurological outcome was assessed using the Glasgow-
Pittsburgh cerebral performance categories (CPC) scale. The good outcome group was defined as a 
CPC 1 or 2, and the poor outcome group as a CPC between 3 and 5. Resuscitated cardiac arrest patients 
whose Glasgow coma scale (GCS) was 8 or less after the return of spontaneous circulation (ROSC), 
and who underwent TTM were included in the study. The exclusion criteria for this study were as 
follows: (1) < 18 y of age, (2) traumatic CA or interrupted TTM (due to haemodynamic instability), (3) 
not eligible for TTM (i.e., intracranial haemorrhage, active bleeding, known terminal illness, or poor 
pre-arrest neurological status), (4) ineligible for LP (i.e., brain computed tomography showed severe 
cerebral oedema, obliteration of the basal cisterns, occult intracranial mass lesion, or coagulopathy: 
platelet count < 40 x 103/mL or international normalized ratio (INR) > 1.5),12 (5) on extracorporeal 
membrane oxygenation, (6) unable to consent to LP, and (7) refusal of further treatment by the next of 
kin.   
2.2. TTM protocol 

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We have applied our protocol and TTM using cooling devices (Arctic Sun ® Energy Transfer Pads TM, 
Medivance Corp., Louisville, USA) for patients who had sustained ROSC since March, 2016. Our 
protocol was as follows; (1)the target temperature of 33°C was maintained for 24 h with rewarming to 
37.0°C at the rate of 0.25°C/h, (2) was monitored using an oesophageal and bladder temperature probe, 
(3) sedatives and analgesics were used during TTM and patients received standard care according to 
the protocol described in a previous study included deep sedation, (4) mild hyperventilation (PaCO2 
35~45 mmHg), (5) mean arterial pressure (MAP) was maintained between 80 and 110 mmHg via 
vasoactive support with norepinephrine and, if needed, plasma volume expansion with crystalloids, (6) 
adequate arterial oxygenation between 150 and 250 mmHg, (7) patients were placed in supine position 
with 30° head-up tilt, (8) anti-epileptic medications were administered as soon as a seizure was 
suspected either clinically or through EEG [13]. 
2.3. Data collection 
The following data were collected from the database: age, sex, presence of a witness at the time of the 
collapse, bystander cardiopulmonary resuscitation (CPR), first monitored rhythm, aetiology of cardiac 
arrest, time from collapse to CPR (no flow time), time from CPR to ROSC (low flow time), sequential 
organ failure assessment (SOF) score, ICP measured on immediate after ROSC, time from ROSC to 
inserting a lumbar drainage catheter placed through the lumbar vertebral interspace into the 
subarachnoid space (ICP time), , and CPC at 6 months after ROSC.  
2.4. ICP control via lumbar CSF drainage  
We have performed the lumbar CSF drainage on the level of the lumbar spine between L3 and L4 with 
the patient lying in the lateral decubitus position with hips and knees flexed. A lumbar drainage catheter 
was inserted using a HermeticTM lumbar accessory kit (Integra Neurosciences, Plainsboro, NJ, USA) in 
the patients. ICP monitoring via lumbar drainage catheter was practiced using the LiquoGuard® (Möller 
Medical GmbH & Co KG, Fulda, Germany). ICP control strategies was initiated when ICP exceeded 
15 mmHg in the absence of noxious stimuli at the rate of 10~20 ml/h via a lumbar drainage catheter 

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25 October 2019 
until ICP was less than 15 mmHg [14, 15].  
2.5. MRI protocol and analysis  
Our hospital has a standardised magnetic resonance imaging (MRI) protocol for non-traumatic 
OHCAs. MRI imaging includes diffusion weighted image (DWI), and apparent diffusion coefficient 
(ADC) map. The MRI was obtained between 72–96 h after ROSC. Forty contiguous DWI sections per 
patient were acquired using a 3T scanner (Achieva 3 T; Philips Medical System, The Netherlands). The 
standard of b=1000 s/mm2 was used for all DWIs. ADC maps were created from the mono-exponential 
calculation of DWI with a commercial software and workstation system (Leonardo MR Workplace; 
Siemens Medical Solutions, Erlangen, Germany). For quantitative analysis of ADC to evaluate the 
effect of lumbar CSF drainage on attenuation of brain swelling, images were processed and analysed 
using software (FMRIB Software Library, Release 5.0 (c) 2012, The University of Oxford) that can 
extract brain tissue by eliminating cranium, optic structure, and extra-cranial soft tissues. Images were 
retrieved in Digital Imaging and Communications in Medicine format from picture archiving and 
communication system servers at the hospital and were converted to NITFI format using MRIcron 
(http://www.nitrc.org/projects/mricron). ADC thresholds ranged from 0 to 1590 X 10-6 mm2/s to exclude 
artefacts or pure CSF [16]. The percentage of voxels (PV) meant number of voxels below different ADC 
thresholds was divided by total number of voxel.  
The % voxels of ADC values (PV) 
PV = 
𝑉𝑜𝑥𝑒𝑙 𝑛𝑢𝑚𝑏𝑒𝑟𝑠 𝑜𝑓 𝐴𝐷𝐶 𝑣𝑎𝑙𝑢𝑒 𝐴𝐷𝐶 𝑡ℎ𝑟𝑒𝑠ℎ𝑜𝑙𝑑
0
𝑉𝑜𝑥𝑒𝑙 𝑛𝑢𝑚𝑏𝑒𝑟𝑠 𝑜𝑓 𝐴𝐷𝐶 𝑣𝑎𝑙𝑢𝑒1590
0
 
2.6. Sample size 
A previous study reported ICP on 24 h after ROSC was 13.22 ± 3.99 mmHg in good outcome and 18.57 
± 5.61 mmHg in poor outcome [17], 62 patients were needed to achieve the power of 0.99 at a 
significance level of 0.05 (two-sided test).  
2.7. Statistical analysis 

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We reported continuous variables as median with interquartile range or as mean and standard deviation 
depending on the normal distribution. Categorical variables were reported as frequencies and 
percentages. We performed the propensity score matching with age, sex, presence of a witness at the 
time of the collapse, bystander CPR, first monitored rhythm, causes of CA, no flow time, low flow time, 
sequential organ failure assessment (SOFA) score, and ICP on immediate after ROSC between both 
groups. Comparisons between the two groups were made using the chi-square test, Fisher's exact test, 
the Mann-Whitney U test, or two-tailed t-test. Multivariate logistic regression models were built to 
identify the effect of the lumbar CSF drainage on the neurologic outcome. Kaplan-Meier analysis was 
performed to evaluate the effect of the lumbar CSF drainage on the neurologic outcome at 6 months 
after ROSC. The estimated odds ratio was considered to assess risk. All statistical analyses were 
performed using the PASW/SPSSTM software, version 18 (IBM Inc., Chicago, USA). Results were 
considered significant at P < 0.05. 
 
 
 
 
 
 
 
 
 
 
 

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25 October 2019 
Conflict of interest statement: The authors have no conflict of interest to report 
Acknowledgements: This work was supported by the National Research Foundation Korea (NRF) grant 
funded by the Korea government (MSIT) (No. 2019R1F1A1041024).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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25 October 2019 
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