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Normobaric oxygen therapy was shown to be effective in reducing post craniotomy pneumocephalus. Theoretical assessment of normobaric oxygen therapy in treating pneumocephalus has shown that a higher level of oxygen concentration will significantly decrease the time for absorption of pneumocephalus. The therapeutic efficacy is not fully established in patients with chronic subdural hematoma after burr hole drainage. Both radiological outcomes and clinical outcomes would be evaluated.
Chronic subdural hematoma (CSDH) is not a benign disease. Morbidity and mortalities were high especially in those with recurrence requiring reoperations. The use of subdural drain after burr hole drainage is an excellent example demonstrating that by reducing CSDH recurrence, a significant improvement in functional outcomes can be observed.
Pneumocephalus is very common after burr hole drainage for CSDH. The use of high-flow oxygen had been reported to be effective in small case series, showing effectiveness in clinical and radiological outcomes. However, no large, prospective, controlled trial has been conducted to establish the efficacy of oxygen therapy on functional outcomes for patients with pneumocephalus after burr hole drainage in CSDH.
Bilateral CSDH has a different prognosis and is associated with a poorer outcome.
In addition to treating pneumocephalus, the use of perioperative oxygen has been suggested to minimize tissue hypoxemia and infection. In a study published in the New England Journal of Medicine, the use of perioperative supplementary oxygen was shown to reduce surgical site infection.
Hyperoxia with oxygen therapy has shown to be safe with minimal changes to the cerebral blood flow (CBF) from functional magnetic resonance imaging (fMRI).
Research Questions
Hypothesis Oxygen therapy for CSDH patients with post-operative pneumocephalus will experience significant resorption of intracranial air within 24 hours. There is a reduction in recurrence rate in terms of the re-operation rates. There is an improvement in functional outcome in terms of mRS.
Aim of the Study To evaluate changes in pneumocephalus volume and functional outcome after oxygen therapy in post-operative CSDH patients treated by burr hole drainage, as compared to the standard care by breathing in room air or low concentration oxygen during the post-operative period.
Study Design Prospective randomized 1:1 parallel-arm study
Methods and Randomization Patients will be recruited when they are considered fit for oxygen therapy as determined by the treating clinician. The timing of burr hole evacuation may vary according to the availability of the emergency operative time slot. The index intervention is postoperative oxygen therapy: 100% normobaric oxygen through a nonrebreather mask (NRM) at 12-15 Litre/minute consecutively for 24 hours. Removal of the nonrebreather mask is allowed during meals or other activities such as physiotherapy. The duration of mask removal would be documented. Compliance with NRM is considered to be good if the mask is kept > 90% of the time during the 24 hours treatment period. The reference intervention is standard post-operative care: the patient would be breathing in normobaric room air. For the reference arm, if the patient has desaturation (i.e. SaO2 < 93%), supplemental O2 therapy can be given to keep SaO2 > 93%. Arterial blood gas would be obtained by the clinicians when deemed necessary. If there is a significant deviation from the study protocol occurs, the patients will be analyzed according to their originally assigned groups (intention-to-treat principle).
Non-rebreather masks, when they are tightly applied, are associated with a lower aerosol dispersion distance (as compared to non-invasive positive pressure ventilation or venturi masks).
Interim data analysis would be performed and the study would be terminated if a significant difference in the primary outcome is observed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High concentration Oxygen Therapy | Experimental | 12-15 Litre/min O2 delivery via Non-Rebreather Mask (NRM) consecutively for 24 hours. |
|
| Room air or low concentration oxygen | Placebo Comparator | Room air or low concentration oxygen (0-2 Litre/min O2 ) consecutively for 24 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High concentration Oxygen therapy | Procedure | FiO2 >80% Oxygen (Delivered with 12-15L/min Non-rebreather Mask) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in the volume of pneumocephalus after 24 hours of oxygen therapy | Volumetric measurement of pneumocephalus from Computed Tomographic (CT) scan for the Head | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Modified Rankins Scale (mRS) | Functional outcomes | at baseline before admission, on admission, at 1 month, at 3 months and at 6 months. |
| EuroQOL EQ-5D | Functional outcomes |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence rate in BILATERAL Chronic Subdural Hematoma (CSDH) | Bilateral (CSDH) | Within six months from the index operation |
| Volumetric reduction in pneumocephalus in BILATERAL Chronic Subdural Hematoma (CSDH) after Oxygen therapy |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David YC Chan, MBBS, FRCS | Contact | 852-35052624 | david.yc.chan@cuhk.edu.hk | |
| Wai S Poon, MBChB, FRCS | Contact | 852-35051316 | wpoon@surgery.cuhk.edu.hk |
| Name | Affiliation | Role |
|---|---|---|
| David YC Chan, MBBS, FRCS | Chinese University of Hong Kong | Principal Investigator |
| Wai S Poon, MBChB, FRCS | Chinese University of Hong Kong | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong | Recruiting | Hong Kong | 852 | Hong Kong |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18447708 | Background | Gore PA, Maan H, Chang S, Pitt AM, Spetzler RF, Nakaji P. Normobaric oxygen therapy strategies in the treatment of postcraniotomy pneumocephalus. J Neurosurg. 2008 May;108(5):926-9. doi: 10.3171/JNS/2008/108/5/0926. | |
| 8602677 | Background | Dexter F, Reasoner DK. Theoretical assessment of normobaric oxygen therapy to treat pneumocephalus. Anesthesiology. 1996 Feb;84(2):442-7. doi: 10.1097/00000542-199602000-00024. |
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| ID | Term |
|---|---|
| D020200 | Hematoma, Subdural, Chronic |
| D012008 | Recurrence |
| D003398 | Craniosynostoses |
| D011007 | Pneumocephalus |
| ID | Term |
|---|---|
| D006408 | Hematoma, Subdural |
| D020198 | Intracranial Hemorrhage, Traumatic |
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
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| Control: Room Air or Low concentration Oxygen | Procedure | FiO2 <30% Oxygen (Delivered with 0-2L/min Nasal Cannula) |
|
| at 1 month, at 3 months and at 6 months. |
| Glasgow Coma Scale (GCS) | Neurological examination | On admission, at 1 month, at 3 months and at 6 months. |
| Recurrence rate, as defined by reoperation rate due to symptomatic recurrence | Surgical complications | Reoperation rate within six months, including the number of re-operations for CSDH during the same admission episode, as well as subsequent readmission for reoperation for CSDH. |
| Changes in brain volume re-expansion | Volumetric measurement from Computed Tomographic (CT) scan for the Head | after 24 hours of oxygen therapy and 1 week after oxygen therapy |
| Changes in volume of subdural fluid | Volumetric measurement from Computed Tomographic (CT) scan for the Head | Recurrence or re-accumulation rate, as measured by an increase in subdural fluid volume at 1 week, 1 month, 3 months, and at 6 months. |
| Incidence of superficial wound infection | Surgical complications | Any surgically associated would infections within 6 months from the index operation |
| Incidence of deep wound infection, including subdural empyema | Surgical complications | Any surgically associated would infections within 6 months from the index operation |
| Incidence of chest complications, including chest infection | Complications | Any complications within the same admission episode for the index operation |
| Any complications arising from the Oxygen therapy (Adverse events) | Complications | Any complications within the same admission episode for the index operation |
| Barthel Index | Functional outcome | at 1 month, 3 months and 6 months |
| PaO2 and PaCO2 from the arterial blood gas (ABG) | Blood taking for ABG when judged to be necessary by the treating physician or when there is desaturation to SaO2 < 93% | During oxygen therapy |
| Duration of stay at the acute neurosurgical ward (LOS) | LOS | During the same admission episode for the index operation |
| Discharge destination | Outcome | Upon the same admission episode for the index operation |
| The length of stay in secondary care | LOS | Upon transferal to the secondary care from the same admission episode for the index operation |
| Mortality rate at 30 days, 3 months and 6 months. | Death rate | at 30 days, 3 months and 6 months. |
Bilateral (CSDH)
| Within 24 hours after Oxygen therapy |
| Improvement in mRS for BILATERAL Chronic Subdural Hematoma (CSDH) | Functional outcome in bilateral CSDH | at 1 month, 3 months and 6 months |
| 10639541 | Background | Greif R, Akca O, Horn EP, Kurz A, Sessler DI; Outcomes Research Group. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med. 2000 Jan 20;342(3):161-7. doi: 10.1056/NEJM200001203420303. |
| 22739621 | Background | Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab. 2012 Oct;32(10):1909-18. doi: 10.1038/jcbfm.2012.93. Epub 2012 Jun 27. |
| 19782872 | Background | Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, Richards HK, Marcus H, Parker RA, Price SJ, Kirollos RW, Pickard JD, Hutchinson PJ. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009 Sep 26;374(9695):1067-73. doi: 10.1016/S0140-6736(09)61115-6. |
| 20868215 | Background | Miranda LB, Braxton E, Hobbs J, Quigley MR. Chronic subdural hematoma in the elderly: not a benign disease. J Neurosurg. 2011 Jan;114(1):72-6. doi: 10.3171/2010.8.JNS10298. Epub 2010 Sep 24. |
| 33419483 | Background | Chan DYC, Poon WS, Chan DTM, Mak WK, Wong GKC. Chronic subdural haematoma during the COVID-19 lockdown period: late presentation with a longer interval from the initial head injury to the final presentation and diagnosis. Chin Neurosurg J. 2021 Jan 8;7(1):4. doi: 10.1186/s41016-020-00229-7. |
| 27914805 | Background | Chan DY, Woo PY, Mak CH, Chu AC, Li CC, Ko NM, Ng SC, Sun TF, Poon WS. Use of subdural drain for chronic subdural haematoma? A 4-year multi-centre observational study of 302 cases. J Clin Neurosci. 2017 Feb;36:27-30. doi: 10.1016/j.jocn.2016.10.039. Epub 2016 Nov 30. |
| 27881024 | Background | Chan DY, Chan DT, Sun TF, Ng SC, Wong GK, Poon WS. The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study. Br J Neurosurg. 2017 Feb;31(1):72-77. doi: 10.1080/02688697.2016.1208806. Epub 2016 Nov 23. |
| Background | Chan DYC, Sun TFD, Poon WS. Steroid for chronic subdural hematoma? A prospective phase IIB pilot randomized controlled trial on the use of dexamethasone with surgical drainage for the reduction of recurrence with reoperation. Chinese Neurosurgical Journal. 2015; 1(1):2. |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006406 | Hematoma |
| D006470 | Hemorrhage |
| D014947 | Wounds and Injuries |
| D013580 | Synostosis |
| D004413 | Dysostoses |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001930 | Brain Injuries |