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The 2023 International Subarachnoid Hemorrhage Conference identified a need to provide an up-to-date review on prevention methods for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage and highlight areas for future research. A PubMed search was conducted for key factors contributing to development of delayed cerebral ischemia: anesthetics, antithrombotics, cerebrospinal fluid (CSF) diversion, hemodynamic, endovascular, and medical management. It was found that there is still a need for prospective studies analyzing the best methods for anesthetics and antithrombotics, though inhaled anesthetics and antiplatelets were found to have some advantages. Lumbar drains should increasingly be considered the first line of CSF diversion when applicable. Finally, maintaining euvolemia before and during vasospasm is recommended as there is no evidence supporting prophylactic spasmolysis or angioplasty. There is accumulating observational evidence, however, that intra-arterial spasmolysis with refractory DCI might be beneficial in patients not responding to induced hypertension. Nimodipine remains the medical therapy with the most support for prevention.
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BACKGROUND AND OBJECTIVE: Early and smooth extubation following anesthesia is an important concern in patients undergoing transsphenoidal pituitary surgery to permit early neurological evaluation and prevent complications. The aim was to compare the RESPONSE FIRST and REVERSAL FIRST techniques for quality of extubation (QOE) in patients undergoing endoscopic transsphenoidal pituitary surgery. METHODS: Fifty-six patients aged 18-60 years, with American Society of Anesthesiologists Physical Statuses I-II, and undergoing transsphenoidal surgery for pituitary tumors were randomized into either the RESPONSE FIRST group, in which neuromuscular reversal was given following the patient's response to oral commands, or the REVERSAL FIRST group, in which reversal of neuromuscular blockade (NMB) was given at the return of spontaneous respiration. QOE was the primary outcome. Hemodynamic response, jugular venous oxygen saturation (SjVO2), time to extubation, and awareness during emergence were assessed as secondary outcomes. RESULTS: The QOE in the RESPONSE FIRST group was significantly better than the REVERSAL FIRST group (mean (interquartile range (IQR)), 18 (17-19) vs 14 (12-14.75), P < 0.001). Heart rate (HR) and mean arterial pressure (MAP) were better in the RESPONSE FIRST group when compared to the REVERSAL FIRST group at the time of extubation, at 5 minutes, and 15 minutes following extubation (P < 0.05). SjVO2values were higher in the REVERSAL FIRST group as compared to the RESPONSE FIRST group during extubation and at 5 minutes after extubation (P < 0.01). There was no significant difference in the time to extubation between the groups (P = 0.73). CONCLUSION: The RESPONSE FIRST technique is associated with better QOE and preservation of systemic and cerebral hemodynamics during extubation in patients undergoing transsphenoidal pituitary surgery when compared to the REVERSAL FIRST technique.
Subject(s)
Airway Extubation , Humans , Adult , Airway Extubation/methods , Middle Aged , Female , Male , Young Adult , Adolescent , Pituitary Neoplasms/surgeryABSTRACT
Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.
Subject(s)
Gene Expression Profiling , Intracranial Aneurysm , Transcriptome , Vasospasm, Intracranial , Humans , Vasospasm, Intracranial/genetics , Vasospasm, Intracranial/metabolism , Intracranial Aneurysm/genetics , Intracranial Aneurysm/metabolism , Intracranial Aneurysm/complications , Transcriptome/genetics , Gene Expression Profiling/methods , Male , Female , Subarachnoid Hemorrhage/genetics , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/metabolism , Gene Expression Regulation , Middle Aged , Aneurysm, Ruptured/genetics , Aneurysm, Ruptured/complicationsABSTRACT
Background: Following aneurysmal subarachnoid hemorrhage, 40-50% of survivors experience cognitive dysfunction, which affects their quality of life. Anesthetic agents play a pivotal role in aneurysm surgeries. However, substantial evidence regarding their effects on neurocognitive function is lacking. This study evaluated the effects of propofol and desflurane on postoperative neurocognitive function and serum S-100B levels. Methods: One hundred patients were equally randomized to receive either propofol (Group P) or desflurane (Group D). Cognitive function was assessed using the Montreal Cognitive Assessment scale at three different time points: Preoperatively, at the time of discharge, and one month after surgery. Perioperative serum levels of S-100B were also measured. Results: The preoperative mean cognitive score in Group P was 21.64 + 4.46 and in Group D was 21.66 + 4.07 (P = 0.79). At discharge, a significant decrease in cognitive scores was observed compared to preoperative scores (Group P- 20.91 + 3.94, P = 0.03 and Group D-19.28 + 4.22, P = 0.00); however, scores were comparable between the two groups (P = 0.09). One month following surgery, mean cognitive scores were 22.63 + 3.57 in Group P and 20.74 + 3.89 in Group D, and the difference was significant (P = 0.04). Higher memory and orientation scores were observed in Group P than in Group D at one month (P < 0.05) in the subgroup analysis. Both groups had similar serum S-100B levels. Conclusion: The mean cognitive scores one month after surgery improved significantly with propofol compared with desflurane, but without clinical significance. Individual domain analysis demonstrated that orientation and memory scores were better preserved with propofol.
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BACKGROUND: Anemia is a common complication of aneurysmal subarachnoid hemorrhage and is associated with unfavorable outcomes. Whether the physiological benefits of transfusion for anemia surpass the risk of blood transfusion remains to be determined. OBJECTIVES: The primary outcome was to evaluate the impact of peri-operative blood transfusion on the long-term neurological outcome, assessed by Glasgow Outcome Scale Extended at 3 months. The secondary outcomes included the impact of transfusion on the short-term neurological outcome, assessed by Modified Rankin Score at discharge/7 days, and on the incidence of vasospasm, infarction, re-exploration, tracheostomy, and length of hospital stay. MATERIAL AND METHODS: This prospective observational study was conducted on 185 patients with aneurysmal subarachnoid hemorrhage undergoing clipping of the aneurysmal neck. In our study, blood transfusion was administered to keep the target Hb around 10 g/dL. RESULTS: Unfavorable long-term outcome was found in 27/97 (28%) of patients who received a blood transfusion as compared to 13/74 (18%) of patients who did not receive a transfusion (P = 0.116). Patients receiving transfusion had more chances of an unfavorable outcome at discharge/7 days as compared to those not transfused [44/103 (43%) versus 22/80 (27%)], P = 0.025. There were increased chances of vasospasm, infarction, re-exploration, tracheostomy, and increased length of hospital stay in patients receiving transfusion (P < 0.05). CONCLUSIONS: The use of blood transfusion in patients with aneurysmal subarachnoid hemorrhage was associated with increased neurological complications and hence an unfavorable short-term outcome. However, when used judiciously as per the clinical requirements, blood transfusion did not have a significant effect on long-term neurological outcome.
Subject(s)
Anemia , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgery , Blood Transfusion , Glasgow Outcome Scale , InfarctionABSTRACT
Delayed cerebral ischemia (DCI) is one of the major causes of a poor neurological outcome following aneurysmal subarachnoid hemorrhage (aSAH). Several biomarkers, including matrix metalloproteinase-9 (MMP-9), have been evaluated to predict the development of DCI for timely management. This prospective cohort study was done on 98 patients with aSAH presenting within 72 h of the ictus. Serum samples were collected preoperatively, 7 days after ictus, 10 days after ictus, or when the patient developed DCI, whichever was earlier. The primary objective was to correlate the serum MMP-9 levels with the development of DCI. The secondary objectives were to correlate the serum MMP-9 levels with sonographic vasospasm and the neurological outcome. There was no correlation between the serum MMP-9 levels and the development of DCI (p = 0.37). Similarly, there was no correlation between the serum MMP-9 levels and the sonographic vasospasm (0.05) nor with the modified Rankin Scale (mRS) at discharge (p = 0.27), mRS at 3 months (p = 0.22), and Glasgow Outcome Scale Extended (GOSE) at 3 months (p = 0.15). Serum MMP-9 levels do not predict the development of DCI following aSAH.
Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Matrix Metalloproteinase 9 , Prospective Studies , Cerebral InfarctionABSTRACT
Enhanced Recovery After Surgery (ERAS) protocols have revolutionized the approach to perioperative care in various surgical specialties. They reduce complications, improve patient outcomes, and shorten hospital lengths of stay. Implementation of ERAS protocols for neurosurgical procedures has been relatively underexplored and underutilized due to the unique challenges and complexities of neurosurgery. This narrative review explores the barriers to, and pioneering strategies of, standardized procedure-specific ERAS protocols, and the importance of multidisciplinary collaboration in neurosurgery and neuroanesthsia, patient-centered approaches, and continuous quality improvement initiatives, to achieve better patient outcomes. It also discusses initiatives to guide future clinical practice, research, and guideline creation, to foster the development of tailored ERAS protocols in neurosurgery.
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Background: Cerebral autoregulation (CA) is crucial for the maintenance of cerebral homeostasis. It can be assessed by measuring transient hyperemic response ratio (THRR) using transcranial Doppler (TCD). We aimed at assessing the incidence of impaired CA (ICA) and its correlation with the neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: One hundred consecutive patients with aSAH scheduled for aneurysmal clipping were enrolled in this prospective and observational study. Preoperative and consecutive 5-day postoperative THRR measurements were taken. Primary objective of the study was to detect the incidence of ICA and its correlation with vasospasm (VS) postclipping, and neurological outcome at discharge and 1, 3, and 12 months was secondary objectives. Results: ICA (THRR < 1.09) was observed in 69 patients preoperatively, 74 patients on the 1st and 2nd postoperative day, 76 patients on 3rd postoperative day, and 78 patients on 4th and 5th postoperative day. Significant VS was seen in 13.4% and 61.5% of patients with intact THRR and deranged THRR, respectively (P < 0.000). Out of 78 patients who had ICA, 42 patients (53.8%) at discharge, 60 patients (76.9%) at 1 month, 54 patients (69.2%) at 3 month, and 55 patients (70.5%) at 12 months had unfavorable neurological outcome significantly more than those with preserved CA. Conclusion: Incidence of ICA assessed in aSAH patients varies from 69% to 78% in the perioperative period. The deranged CA was associated with significantly poor neurological outcome. Therefore, CA assessment using TCD-based THRR provides a simple, noninvasive bedside approach for predicting neurological outcome in aSAH.
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Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.
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Introduction: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that progressively leads to motor neuron degeneration at the neuromuscular junctions, resulting in paralysis in the patients. The clinical diagnosis of ALS is time taking and further delays the therapeutics that can be helpful if the disease is diagnosed at an early stage. Changes in plasma composition can be reflected upon CSF composition and hence, can be used to study the diagnosis and prognosis markers for the disease. Aim: To develop a simple model system using motor neuron like cell line after plasma induction. Method: Neuroblastoma × Spinal Cord hybridoma cell line (NSC34) was cultured under appropriate conditions. 10% ALS patients' plasma was added to the media, and cells were conditioned for 12 h. Cell survival analysis and differential gene expression of a panel of molecules (published previously, VEGF, VEGFR2, ANG, OPTN, TDP43, and MCP-1) were done. Results: ALS patients' plasma impacted the life of the cells and reduced survival to nearly 50% after induction. VEGF was found to be significantly down-regulated in the cells, which can be explained as a reason for reduced cell survival. Conclusion: ALS plasma altered the expression of an essential neuroprotective and growth factor VEGF in NSC34 cells leading to reduced viability.
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BACKGROUND: The effects of ketofol (propofol and ketamine admixture) on systemic hemodynamics and outcomes in patients undergoing emergency decompressive craniectomy for traumatic brain injury (TBI) are unknown and explored in this study. METHODS: Fifty patients with moderate/severe TBI were randomized to receive ketofol (n=25) or propofol (n=25) for induction and maintenance of anesthesia during TBI surgery. Intraoperative hemodynamic stability was assessed by continuous measurement of mean arterial pressure (MAP) and need for rescue interventions to maintain MAP within 20% of baseline. Brain relaxation scores, serum biomarker-glial fibrillary acidic protein levels, and extended Glasgow Outcome Scale (GOSE) at 30 and 90 days after discharge were also explored. RESULTS: MAP was lower and hemodynamic fluctuations more frequent in patients receiving propofol compared with those receiving ketofol (P<0.05). MAP fell >20% below baseline in 22 (88%) patients receiving propofol and in 10 (40%) receiving ketofol (P=0.001), with a greater requirement for vasopressors (80% vs. 24%, respectively; P=0.02). Intraoperative brain relaxation scores and GOSE at 30 and 90 day were similar between groups. Glial fibrillary acidic protein was lower in the ketofol group (3.31±0.43 ng/mL) as compared with the propofol (3.41±0.17 ng/mL; P=0.01) group on the third postoperative day. CONCLUSION: Compared with propofol, ketofol for induction and maintenance of anesthesia during decompressive surgery in patients with moderate/severe TBI was associated with improved hemodynamic stability, lower vasopressor requirement, and similar brain relaxation.
Subject(s)
Anesthetics, Intravenous , Brain Injuries, Traumatic , Ketamine , Propofol , Humans , Anesthetics, Intravenous/therapeutic use , Brain Injuries, Traumatic/surgery , Brain Injuries, Traumatic/drug therapy , Glial Fibrillary Acidic Protein , Propofol/therapeutic use , Prospective Studies , Vasoconstrictor Agents/therapeutic use , Ketamine/therapeutic useABSTRACT
Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10-4), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10-8) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment.
Subject(s)
Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Genome-Wide Association Study , Longitudinal Studies , Treatment OutcomeABSTRACT
BACKGROUND: Studies have evaluated the effects of volatile and intravenous anesthetic agents on the cerebral vasculature with inconsistent results. We used digital subtraction angiography to compare the effects of propofol and sevoflurane on the luminal diameter of cerebral vessels and on cerebral transit time in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This prospective preliminary study included adult patients with good-grade aSAH scheduled for endovascular coil embolization; patients were randomized to receive propofol or sevoflurane anesthesia during endovascular coiling. The primary outcome was the luminal diameter of 7 cerebral vessel segments measured on the diseased and nondiseased sides of the brain at 3 time points: awake, postinduction of anesthesia, and postcoiling. Cerebral transit time was also measured as a surrogate for cerebral blood flow. RESULTS: Eighteen patients were included in the analysis (9 per group). Baseline and intraoperative parameters were similar between the groups. Propofol increased the diameter of 1 vessel segment at postinduction and postcoiling on the diseased side and in 1 segment at postcoiling on the nondiseased side of the brain ( P <0.05). Sevoflurane increased vessel diameter in 3 segments at postinduction and in 2 segments at postcoiling on the diseased side, and in 4 segments at postcoiling on the nondiseased side ( P <0.05). Cerebral transit time did not change compared with baseline awake state in either group and was not different between the groups. CONCLUSIONS: Sevoflurane has cerebral vasodilating properties compared with propofol in patients with good-grade aSAH. However, sevoflurane affects cerebral transit time comparably to propofol.
Subject(s)
Anesthetics, Inhalation , Intracranial Aneurysm , Methyl Ethers , Propofol , Subarachnoid Hemorrhage , Adult , Humans , Propofol/pharmacology , Sevoflurane , Intracranial Aneurysm/therapy , Angiography, Digital Subtraction , Prospective Studies , Anesthetics, Intravenous/pharmacologyABSTRACT
Objectives The choice of inhalational or intravenous anesthetic agents is debatable in neurosurgical patients. Desflurane, a cerebral vasodilator, may be advantageous in ischemic cerebral pathologies. Hence, we planned to compare desflurane and propofol in patients with moyamoya disease (MMD) with the objective of comparing neurological outcomes. Materials and Methods This prospective pilot trial was initiated after institutional ethics committee approval. Patients with MMD undergoing revascularization surgery were randomized into two groups receiving either desflurane or propofol intraoperatively. Neurological outcomes were assessed using a modified Rankin score (mRS) at discharge and an extended Glasgow outcome score (GOS-E) at 1 month. Intraoperative parameters, including hemodynamic parameters, end-tidal carbon dioxide, entropy, intraoperative brain relaxation scores (BRS), and rescue measures for brain relaxation, were compared. Statistical Analysis The normality of quantitative data was checked using Kolmogorov-Smirnov tests of normality. Normally distributed data were compared using unpaired t -tests, skewed data using Mann-Whitney U tests, and categorical variables using chi-squared tests. Results A total of 17 patients were randomized, 10 in the desflurane and 7 in the propofol group. mRS (1.3 ± 0.6 and 1.14 ± 0.4, p = 0.450) and GOS-E (6.7 ± 0.6 and 6.85 ± 0.5, p = 0.45) were comparable between desflurane and propofol groups, respectively. BRS was significantly higher in the desflurane group (3.6 ± 0.5) compared to the propofol group (2.1 ± 0.3, p = 0.001), with a significant number of patients requiring rescue measures in the desflurane group (70%, p < 0.001). Other outcome parameters were comparable ( p > 0.05). Conclusion We conclude that postoperative neurological outcomes were comparable with using either an anesthetic agent, desflurane, or propofol in MMD patients undergoing revascularization surgery. Maintenance of anesthesia with propofol had significantly superior surgical field conditions.
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It is estimated that 50% of patients with coronavirus disease 2019 (COVID-19) have varying degrees of renal involvement. In this clinical biomarker development research, we examined in a retrospective study design the temporal changes in biochemical laboratory parameters in relation to the development of acute kidney injury (AKI). In a sample of 399 patients admitted from May 2020 to May 2021 to a tertiary health care intensive care unit (ICU), the incidence of AKI was 27.3%, and the median time to AKI was on 7th day of ICU admission. Most common etiology of AKI was kidney hypoperfusion. Within 72 h of developmental of low blood pressure, 63.76% developed AKI. The likelihood of AKI was higher in those with elevated serum ferritin, aspartate transaminase, and thrombocytopenia (low platelet count). A cutoff value of 750.3 ng/mL [area under the ROC curve (AUC) = 0.777] for serum ferritin, and 40.05 U/L for alanine aminotransferase (AUC = 0.677) 1 day before development of AKI displayed, respectively, a sensitivity of 76.2% and 64.3%, whereas the specificity was 69.5% and 64.1%, respectively, for these two biochemical predictors. A cutoff value of platelets (152.50 × 109/L [AUC = 0.75]) measured 4 days before development of AKI, displayed 83.3% sensitivity and 16.4% specificity. Taken together, our study thoroughly examined the temporal association of various clinical and laboratory parameters with AKI and prediction models were developed as per results of the time series data. These observations in a tertiary health care setting contribute to ongoing efforts for biomarker discovery and development using routine biochemical tests so as to forecast AKI in patients with COVID-19.
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Acute Kidney Injury , COVID-19 , Humans , Retrospective Studies , COVID-19/complications , ROC Curve , Critical Illness , Acute Kidney Injury/etiology , Acute Kidney Injury/epidemiology , BiomarkersABSTRACT
Background: Stellate ganglion block (SGB) causes blockage of sympathetic nerve activity, which may lead to intracerebral vessel dilatation and relieve cerebral vasospasm in patients of aneurysmal subarachnoid hemorrhage (aSAH). Objective: The aim of this study was to evaluate the efficacy and safety of SGB to relieve cerebral vasospasm on clinicoradiological parameters. Materials and Methods: We prospectively included 20 patients with clinical and angiographic evidence of vasospasm post aneurysmal clipping. Cerebral blood flow velocity and Lindegaard ratio were assessed using transcranial Doppler (TCD). Location of vasospasm, vessel diameter, vasospasm severity, parenchymal filling time, and venous sinus filling time were assessed on digital subtraction angiography (DSA). Patients received ultrasound-guided SGB with 10 mL of 0.5% bupivacaine on the ipsilateral side of the vasospasm. After 30 minutes, the neurological status, TCD, and DSA parameters were reevaluated. Results: After SGB, there was statistically significant reduction in the middle cerebral artery (MCA) peak systolic velocity (P = 0.005), mean flow velocity (P = 0.025), and Lindegaard ratio (P = 0.022) on TCD. We observed significant dilatation in the mean vessel diameter measured at the mid-M1 segment of MCA (P = 0.003) and mid-A1 segment of ACA (P = 0.002) on DSA. The mean parenchymal filling time and mean venous sinus filling time decreased nonsignificantly after SGB (P = 0.163/0.104). Neurological improvement was observed in five (25%) patients. Conclusion: SGB has positive clinicoradiological influence in the management of cerebral vasospasm of large vessels. However, its effect on cerebral microvasculature is limited and needs a larger database for further analysis.
Subject(s)
Subarachnoid Hemorrhage , Vasospasm, Intracranial , Cerebrovascular Circulation , Humans , Prospective Studies , Stellate Ganglion/diagnostic imaging , Stellate Ganglion/surgery , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgery , Ultrasonography, Doppler, Transcranial/adverse effects , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/therapyABSTRACT
Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.
Subject(s)
Subarachnoid Hemorrhage , Genome-Wide Association Study , Genotype , Humans , Meta-Analysis as Topic , Polymorphism, Single Nucleotide/genetics , Prognosis , Subarachnoid Hemorrhage/geneticsABSTRACT
BACKGROUND: Fluid imbalance is common after aneurysmal subarachnoid hemorrhage and negatively impacts clinical outcomes. We compared intraoperative goal-directed fluid therapy (GDFT) using left ventricular outflow tract velocity time integral (LVOT-VTI) measured by transesophageal echocardiography with central venous pressure (CVP)-guided fluid therapy during aneurysm clipping in aneurysmal subarachnoid hemorrhage patients. METHODS: Fifty adults scheduled for urgent craniotomy for aneurysm clipping were randomly allocated to 2 groups: group G (n=25) received GDFT guided by LVOT-VTI and group C (n=25) received CVP-guided fluid management. The primary outcome was intraoperative mean arterial pressure (MAP). Secondary outcomes included volume of fluid administered and several other intraoperative and postoperative variables, including neurological outcome at hospital discharge and at 30 and 90 days. RESULTS: There was no difference in MAP between the 2 groups despite patients in group G receiving lower volumes of fluid compared with patients in group C (2503.6±534.3 vs. 3732.8±676.5 mL, respectively; P <0.0001). Heart rate and diastolic blood pressure were also comparable between groups, whereas systolic blood pressure was higher in group G than in group C at several intraoperative time points. Other intraoperative variables, including blood loss, urine output, and lactate levels were not different between the 2 groups. Postoperative variables, including creatinine, duration of postoperative mechanical ventilation, length of intensive care unit and hospital stay, and incidence of acute kidney injury, pneumonitis, and vasospasm were also comparable between groups. There was no difference in neurological outcome at hospital discharge (modified Rankin scale) and at 30 and 90 days (Extended Glasgow Outcome Scale) between the 2 groups. CONCLUSION: Compared with CVP-guided fluid therapy, transesophageal echocardiography-guided GDFT maintains MAP with lower volumes of intravenous fluid in patients undergoing clipping of intracranial aneurysms with no adverse impact on postoperative complications.
Subject(s)
Intracranial Aneurysm , Subarachnoid Hemorrhage , Adult , Craniotomy , Fluid Therapy , Goals , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/surgery , Prospective Studies , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgeryABSTRACT
BACKGROUND: The use of nonsteroidal anti-inflammatory drugs in neurosurgery remains controversial because of potential risk of hematoma formation secondary to platelet dysfunction. This study aimed to investigate the efficacy and safety of diclofenac compared with paracetamol for the management of postcraniotomy pain. METHODS: In all, 110 adult patients undergoing craniotomy for supratentorial tumors were randomized to receive either intravenous paracetamol (15 mg/kg) or intravenous diclofenac sodium (1.5 mg/kg) 30 minutes before the end of surgery and postoperatively at 12-hour intervals up to 48 hours. The analgesic efficacy of diclofenac and paracetamol was assessed using the Numerical Rating Scale (NRS) score at 12, 24, and 48 hours after surgery. We also examined the need for rescue analgesia, coagulation profiles using a Sonoclot analyzer, and incidence of intracranial hematoma formation. RESULTS: At 24 hours postsurgery, NRS scores were lower in group D than in group P; median (interquartile range) and mean rank NRS score in group D was 3.00 (1.0), 43.71, respectively, compared with 3.00 (1.0), 59.29 in group P (P=0.004). Patients in group P received more rescue analgesia than those in group D. Coagulation profiles were similar between groups at 24 hours. Activated clotting time was longer in group D (128.76±12.61 s) than in group P (123.84±09.77 s; P=0.03) at 48 hours, although remained within normal limits in both groups; clot rate and platelet function were similar at 48 hours. There was no difference in the incidence of postoperative tumor bed hematoma. CONCLUSION: Compared with paracetamol, diclofenac sodium provided more effective postoperative analgesia at 24 hours with no evidence of adverse effects on coagulation profiles in patients undergoing craniotomy for supratentorial tumors.