Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial.

BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Clinical outcome after microsurgical resection of intraventricular trigone meningiomas: a single-centre analysis of 20 years and literature overview.

BACKGROUND: Outcome and treatment-associated morbidity analysis of trigone meningioma surgery. METHODS: We retrospectively assessed 27 neurosurgically treated patients (median age 63 years, range 15-84) between 1999 and 2019. The median preoperative Karnofsky Performance Scale (KPS) was 80 (range 20-100), and the majority (78%) suffered from tumour-specific symptoms. The most frequent symptoms were aphasia (n = 6), visual field deficits (n = 5), and increased intracranial pressure (n = 5). The median tumour volume was 11.2 cm3 (range 3.9-220.5). The most common approaches were the transtemporal (n = 17) and transparietal routes (n = 5). RESULTS: At last follow-up (median follow-up 35 months, range 3-127), the median KPS was 90 (range 30-100); eleven (42%) patients had improved, nine (35%) were unchanged, six (23%) had worsened, and one was lost to follow-up. One year after surgery, 18/21 (86%) patients had retained an activity level similar or improved compared with preoperatively. No surgery-related mortality was recorded. Postoperative new neurological deficits were seen in 13 (48%) patients; eight suffered from permanent, most commonly motor deficits (n = 4), and five of transient deficits. Permanent new motor deficits improved in the majority of affected patients (3/4) over time. New deficits were more often seen for transtemporal (8/17) than transparietal approaches (1/5). Patients with postoperative permanent new deficits had a significantly worse KPS at last follow-up (p < 0.001). CONCLUSIONS: The transtemporal and transparietal approaches provide good access, but the latter might provide for a better risk profile. Patients show favourable outcome, but there is a considerable risk for new neurological deficits. This must be taken into consideration for oligosymptomatic patients.

Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus.

UNLABELLED: BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site. METHODS: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. RESULTS: Four of the 17 patients (23.5%) had amyloid-ß pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-ß levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-ß level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%. CONCLUSIONS: [(18)F]Flutemetamol detects brain amyloid-ß in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). METHODS: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. RESULTS: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). DISCUSSION: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.

Incidence of surgery for chronic subdural hematoma in Finland during 1997-2014: a nationwide study.

OBJECTIVE: The number of surgeries performed for chronic subdural hematoma (CSDH) has increased. However, these changes have been poorly reported. The authors aimed to assess the national incidence of surgeries for CSDH in Finland during an 18-year time period from 1997 to 2014. They hypothesized that the incidence of CSDH surgeries has continued to increase, particularly among the elderly. METHODS: A nationwide register-based follow-up study was performed using the Finnish Care Register for Health Care. All adult patients undergoing primary CSDH surgeries during 1997-2014 were included. The study population was followed up from the time of CSDH surgery until death or the end of follow-up on December 31, 2017. The incidences of CSDH surgery per 100,000 person-years were calculated separately in each age group and sex. Age standardization was performed for those 20 years of age and older with weights from the 2013 European Standard Population. Negative binomial regression models were used to assess changes in incidence rate ratios (IRRs) during the study period. RESULTS: In total, 9280 patients were identified. The age-standardized incidence of CSDH surgery increased from 12.2 to 16.5 per 100,000 person-years during 1997-2014. The age- and sex-adjusted incidence of CSDH surgery increased by 30% (IRR 1.30, 95% CI 1.20-1.41). The age- and sex-adjusted incidence increased more in the older age groups, with an IRR of 1.24 for those aged 60-69 years, 1.32 for those 70-79 years, 1.46 for those 80-89 years, and 1.85 for those aged 90 years or older. The adjusted incidence did not increase for those aged 18-59 years. The sex difference (2:1 men/women) was consistent throughout the study period, with a higher incidence among men. One year after the primary surgery, 19% of the population had a resurgery, and the 1-year case fatality rate was 15%. The median age of patients increased from 73 to 76 years. CONCLUSIONS: During the past 2 decades, the age- and sex-adjusted incidence of CSDH surgery has increased in Finland, with major increases for those aged 60 years or older. This increase is likely to continue in parallel with the aging population and increased life expectancies.

Microsurgical removal of a misplaced intraspinal venous stent in a patient with inferior vena cava atresia.

Inferior vena cava atresia (IVCA) is a rare vascular condition that may be treated by venous stenting. The authors report on the microsurgical removal of an intraspinally misplaced stent causing nerve root compression and neurological deficits.A 42-year-old patient with IVCA and painful cutaneous collaterals had been scheduled for treatment by stenting of the iliocaval confluence and associated venous collaterals. Initial stenting of the right iliac vein was successful; however, during recanalization of the left paravertebral plexus, the stent entered the spinal canal via extraspinal-to-intraspinal venous collaterals. Because of the use of monoplanar angiography, the stent misplacement was not seen during the procedure. Postinterventionally, the patient experienced a foot elevation weakness (grade 1/5) as well as pain and hypesthesia corresponding to the L5 dermatome. Ultrasonography ruled out a lumbosacral plexus hematoma. CT angiography showed that a stent had entered the spinal canal through the left S1 neuroforamen causing nerve root compression. The intraspinal portion of the stent was removed piecemeal via a left-sided hemilaminectomy. Venous bleeding due to the patient's anticoagulation therapy, the stent's sharp mesh wire architecture, and the proximity to nerve roots complicated the surgery. Postoperatively, the foot elevation improved to grade 4/5.

Finnish study of intraoperative irrigation versus drain alone after evacuation of chronic subdural haematoma (FINISH): a study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Chronic subdural haematomas (CSDHs) are one of the most common neurosurgical conditions. The goal of surgery is to alleviate symptoms and minimise the risk of symptomatic recurrences. In the past, reoperation rates as high as 20%-30% were described for CSDH recurrences. However, following the introduction of subdural drainage, reoperation rates dropped to approximately 10%. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural drainage. Yet, the role of intraoperative irrigation has not been established. If there is no difference in recurrence rates between intraoperative irrigation and no irrigation, CSDH surgery could be carried out faster and more safely by omitting the step of irrigation. The aim of this multicentre randomised controlled trial is to study whether no intraoperative irrigation and subdural drainage results in non-inferior outcome compared with intraoperative irrigation and subdural drainage following burr-hole craniostomy of CSDH. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, parallel group, non-inferiority multicentre trial comparing single burr-hole evacuation of CSDH with intraoperative irrigation and evacuation of CSDH without irrigation. In both groups, a passive subdural drain is used for 48 hours as a standard of treatment. The primary outcome is symptomatic CSDH recurrence requiring reoperation within 6 months. The predefined non-inferiority margin for the primary outcome is 7.5%. To achieve a 2.5% level of significance and 80% power, we will randomise 270 patients per group. Secondary outcomes include modified Rankin Scale, rate of mortality, duration of operation, length of hospital stay, adverse events and change in volume of CSDH. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District (HUS/3035/2019 §238) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04203550.

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case-control comparison with family members.

BACKGROUND: The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. METHODS: Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. RESULTS: Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). CONCLUSIONS: Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.

Transition of a Clinical Practice to Use of Subdural Drains after Burr Hole Evacuation of Chronic Subdural Hematoma: The Helsinki Experience.

BACKGROUND: A number of randomized controlled trials have shown the benefit of drain placement in the operative treatment of chronic subdural hematoma (CSDH); however, few reports have described real-life results after adoption of drain placement into clinical practice. We report the results following a change in practice at Helsinki University Hospital from no drain to subdural drain (SD) placement after burr hole craniostomy for CSDH. METHODS: We conducted a retrospective observational study of consecutive patients undergoing burr hole craniostomy for CSDH. We compared outcomes between a 6-month period when SD placement was arbitrary (July-December 2015) and a period when SD placement for 48 hours was routine (July-December 2017). Our primary outcome of interest was recurrence of CSDH necessitating reoperation within 6 months. Patient outcomes, infections, and other complications were assessed as well. RESULTS: A total of 161 patients were included, comprising 71 (44%) in the drain group and 90 (56%) in the non-drain group. There were no significant differences in age, comorbidities, history of trauma, or use of antithrombotic agents between the 2 groups (P > 0.05 for all). Recurrence within 6 months occurred in 18% of patients in the non-drain group, compared with 6% in the drain group (odds ratio, 0.28; 95% confidence interval, 0.09-0.87; P = 0.028). There were no differences in neurologic outcomes (P = 0.72), mortality (P = 0.55), infection rate (P = 0.96), or other complications (P = 0.20). CONCLUSIONS: The change in practice from no drain to use of an SD after burr hole craniostomy for CSDH effectively reduced the 6-month recurrence rate with no effect on patient outcomes, infections, or other complications.

Finnish Trial on Practices of Anterior Cervical Decompression and Fusion (FACADE): a protocol for a prospective randomised non-inferiority trial comparing outpatient versus inpatient care.

INTRODUCTION: Although a great majority of patients with cervical radiculopathy syndrome can successfully be treated non-operatively, a considerable proportion experience persistent symptoms, severe enough to require neurosurgical intervention. During the past decade, cervical spine procedures have increasingly been performed on an outpatient basis and retrospective database analyses have shown this to be feasible and safe. However, there are no randomised controlled studies comparing outpatient care with inpatient care, particularly with emphasis on the patients' perception of symptom relief and their ability to return to normal daily activities and work. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, parallel group non-inferiority trial comparing the traditional hospital surveillance (inpatient, patients staying in the hospital for 1-3 nights after surgery) with outpatient care (discharge on the day of the surgery, usually within 6-8 hours after procedure) in patients who have undergone anterior cervical decompression and fusion procedure. To determine whether early discharge (outpatient care) is non-inferior to inpatient care, we will randomise 104 patients to these two groups and follow them for 6 months using the Neck Disability Index (NDI) as the primary outcome. We expect that early discharge is not significantly worse than the current care in terms of change in NDI. Non-inferiority will be declared if the mean improvement for outpatient care is no worse than the mean improvement for inpatient care, by a margin of 17.3%. We hypothesise that a shorter hospital stay results in more rapid return to normal daily activities, shorter duration of sick leave and decreased secondary costs to healthcare system. Secondary outcomes in our study are arm pain and neck pain using the Numeric Rating Scale, operative success (Odom's criteria), patient's satisfaction to treatment, general quality of life (EQ-5D-5L), Work Ability Score, sickness absence days, return to previous leisure activities and complications. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District on 6 June 2019 (1540/2019) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03979443.

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH.

OBJECTIVE: To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. METHODS: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. RESULTS: The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. CONCLUSIONS: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.

Desmoplastic infantile ganglioglioma: novel aspects in clinical presentation and genetics.

BACKGROUND: Desmoplastic infantile ganglioglioma is a rare tumor occurring mainly in infants and young children. Both radiological and histopathological appearances may resemble malignancy, although its clinical course is mainly benign. METHODS: Altogether, 5 cases of DIG have been operated on in our hospital since the first diagnosis of DIG in Finland in 1993. We evaluated their presenting symptoms, radiological and surgical findings, histologic characteristics, and follow-up. RESULTS: All patients were male. Three were less than 18 months old, and 2 were 35 and 79 months old. The most common presenting symptoms were epileptic seizures (4 cases). In 4 cases, there was a histopathologically verified single cystic tumor. In 1 case, DIG was operatively diagnosed in 2 separate locations. This patient, moreover, had 2 other lesions suspected of being DIG, including a mass originating from the ophthalmic nerve. None of the patients received adjuvant therapies. All our patients are alive after 7 to 120 months of follow-up. There were no recurrences in any of the patients after tumor resection. For the first time, we describe EGFR and MYCN amplifications in tumors which are, respectively, of their mixed glial and neuronal origin. CONCLUSION: The clinical presentation of DIG may be more often associated with epileptic seizures than previously thought. The radiological appearance of DIG may vary from cystic to solid and from contrast-enhancing to nonenhancing. Even multiple locations of DIG have been encountered. Increasing evidence supports surgery as the treatment of choice for DIG, although oncogene amplifications have been described.

Familial idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE ε4 genotype. This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH.

Therapeutic hypothermia after cardiac arrest - cerebral perfusion and metabolism during upper and lower threshold normocapnia.

BACKGROUND: During cardiac arrest and after successful resuscitation a continuum of ischaemia-reperfusion injury develops. Mild hypothermia exerts protective effects in the postresuscitation phase but also alters CO2 production and solubility, which may lead to deleterious effects if overlooked when adjusting the ventilation of the resuscitated patient. Using a multimodality approach, the effects of different carbaemic states on cerebral perfusion and metabolism were evaluated during therapeutic hypothermia. METHODS: Eight comatose survivors of prehospital cardiac arrest were cooled to 33°C for 24 h and underwent a 60 min phase of interventional lower threshold normocapnia according to temperature non-corrected pCO2 (4.2 kPa) and higher threshold normocapnia according to corrected pCO2 (6.0 kPa) in a random order. Prior to, during and after each phase, cerebral perfusion and metabolites via a microdialysis catheter were measured. RESULTS: During upper-threshold pCO2, an increase in middle cerebral artery mean flow velocity (MFV) and jugular bulb oxygen saturation (jSvO2) were observed with a concomitant decrease in cerebral lactate concentration. Lower threshold normocapnia was associated with a decrease in MFV in most patients. In all patients jSvO2 decreased but no change in cerebral lactate was observed. In seven patients jSvO2 decreased below 55%. These changes were not reflected to intracranial pressure or cerebral oximetry. CONCLUSIONS: During induced hypothermia, lower threshold normocapnia was associated with decreased cerebral perfusion/oxygenation but not reflected to interstitial metabolites. Upper threshold pCO2 increased cerebral perfusion and reduced cerebral lactate. Vigilance over the ventilatory and CO2 analysis regimen is mandatory during mild hypothermia.