Course of Headaches and Predictive Factors Associated With Analgesia Failure Following Spontaneous Subarachnoid Hemorrhage: A Prospective Cohort Study.

BACKGROUND: Headache is the most common presenting symptom of spontaneous subarachnoid hemorrhage and managing this acute pain can be challenging. The aim of this study was to describe the course of headaches and factors associated with analgesic failure in patients with spontaneous subarachnoid hemorrhage. METHODS: We conducted a prospective observational study in patients admitted to a neurocritical care unit (between April 2016 and March 2017) within 48 hours of spontaneous subarachnoid hemorrhage. Headache intensity was assessed using a Numerical Pain Rating Scale (NPRS) ranging from 0 to 10. Analgesic failure was defined as any day average NPRS score >3 after 72 hours of hospitalization despite analgesic treatment. RESULTS: Sixty-three patients were included in the analysis. Thirty-six (56.25%) patients experienced at least 1 episode of severe headache (NPRS ≥7), and 40 (63.5%) patients still reported moderate to severe headache on the final day of the study (day 12). Forty-six (73.0%) patients required treatment with opioids and 37 (58.7%) experienced analgesic failure. Multivariable analysis showed that analgesic failure was associated with smoking history (odds ratio [OR]=4.31, 95% confidence interval [CI]: 1.23-17.07; P =0.027), subarachnoid blood load (OR=1.11, 95% CI: 1.01-1.24; P =0.032) and secondary complications, including rebleeding, hydrocephalus, delayed cerebral ischemia, hyponatremia, or death (OR=4.06, 95% CI: 1.17-15.77; P =0.032). CONCLUSIONS: Headaches following spontaneous subarachnoid hemorrhage are severe and persist during hospitalization despite standard pain-reducing strategies. We identified risk factors for analgesic failure in this population.

Nicotine Replacement Therapy Does Not Reduce Headaches Following Subarachnoid Hemorrhage: A Propensity Score-Matched Study.

BACKGROUND: A significant number of patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) are active smokers and are at risk of developing nicotine withdrawal symptoms (e.g., cravings, irritability, insomnia, headaches, etc.). This study aimed to evaluate the use of nicotine replacement therapy (NRT) regarding headache severity and analgesics consumption. METHODS: A retrospective study was conducted using prospectively collected data from 2014 to 2019 in the neurointensive care unit of the Hospices Civils in Lyon, France. We performed a propensity score matching analysis. The covariables used were age, sex, initial World Federation of Neurosurgical Societies score, Hijdra sum score, and factors associated with pain following aSAH (history of chronic pain, anxiety, or depression). Smokers received NRT through a transdermal device. The primary end point was headache control. Secondary end points were mean numerical pain rating scale score and analgesics consumption. RESULTS: One hundred and fifty-five patients were included among 523 patients hospitalized for aSAH. Fifty-one patients underwent nicotine substitution and were matched to 51 unsubstituted patients. The headache control rate was not different between the two groups (43.1% vs. 31.4%, p = 0.736). The mean numeric pain rating scale score in the substituted group was 2.2 (1.1-3.5) and 2.4 (1.6-3.1) in the unsubstituted group (p = 0.533). The analgesics consumption (acetaminophen, tramadol, and morphine) was the same in the two groups. CONCLUSIONS: The use of NRT in the acute phase of aSAH does not seem to have an impact on the intensity of headaches or analgesics consumption.

Amount of blood during the subacute phase and clot clearance rate as prognostic factors for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) is a poorly predictable complication occurring after aneurysmal subarachnoid hemorrhage (SAH) that can have dramatic functional consequences. Identifying the patients with the highest risk of DCI may help to institute more suitable monitoring and therapy. Early brain injuries and aneurysm-securing procedure complications could be regarded as confounding factors leading to severity misjudgment. After an early resuscitation phase, a subacute assessment may be more relevant to integrate the intrinsic SAH severity. A retrospective analysis was performed upon patients prospectively included in the registry of SAH patients between July 2015 to April 2020. The amount of cisternal and intraventricular blood were assessed semi-quantitatively on acute and subacute CT scans performed after early resuscitation. A clot clearance rate was calculated from their comparison. The primary endpoint was the occurrence of a DCI. A total of 349 patients were included in the study; 80 (22.9%) experienced DCI. In those patients, higher Fisher grades were observed on acute (p = 0.026) and subacute (p = 0.003) CT scans. On the subacute CT scan, patients who experienced DCI had a higher amount of blood, either at the cisternal (median Hijdra sum score: 11 vs 5, p < 0.001) or intraventricular (median Graeb score: 4 vs 2, p < 0.001) level. There was a negative linear relationship between the cisternal clot clearance rate and the risk of DCI. The assessment of the amount of subarachnoid blood and clot clearance following resuscitation after aneurysmal SAH can be useful for the prediction of neurological outcome.

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate could better characterize blood-brain barrier damage and refine the delivery of neuroprotective agents. We previously developed an original endovascular stroke model of acute ischaemic stroke treated by mechanical thrombectomy followed by positron emission tomography-magnetic resonance imaging. Cerebral capillary permeability was quantified for two molecule sizes: small clinical gadolinium Gd-DOTA (<1 nm) and AGuIX® nanoparticles (∼5 nm) used for brain theranostics. On dynamic contrast-enhanced magnetic resonance imaging, the baseline transfer constant K trans was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] ×10-3 min-1, respectively, in the normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] ×10-3 min-1 in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, K trans for both Gd-DOTA and AGuIX® nanoparticles was significantly higher within the ischaemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] ×10-3 min-1 for Gd-DOTA and AGuIX® nanoparticles, respectively. With AGuIX® nanoparticles, K trans also increased within the ischaemic growth areas, suggesting added value for AGuIX®. Finally, K trans was significantly lower in both the lesion and the choroid plexus in a drug-treated group (ciclosporin A, n = 7) compared to placebo (n = 5). K trans quantification with AGuIX® nanoparticles can monitor early blood-brain barrier damage and treatment effect in ischaemic stroke after reperfusion.

Marked EEG worsening following Levetiracetam overdose: How a pharmacological issue can confound coma prognosis.

Levetiracetam is an anti-epileptic drug commonly used in intensive care when seizure is suspected as a possible cause of coma. We propose to question the cofounding effect of Levetiracetam during the prognostication process in a case of anoxic coma. We report the story of a young woman presenting a comatose state following a hypoxic cardiac arrest. After a first EEG presenting an intermediate EEG pattern, a seizure suspicion led to prescribe Levetiracetam. The EEG showed then the appearance of burst suppression, which was compatible with a very severe pattern of post-anoxic coma. This aggravation was in fact related to an overdose of Levetiracetam (the only medication introduced recently) and was reversible after Levetiracetam cessation. The increased plasmatic dosages of Levetiracetam confirming this overdose could have been favoured by a moderate reduction of renal clearance, previously underestimated because of a low body-weight. This EEG dynamic was unexpected under Levetiracetam and could sign a functional instability after anoxia. Burst suppression is classically observed with high doses of anaesthetics, but is not expected after a minor anti-epileptic drug. This report proposes that Levetiracetam tolerance might not be straightforward after brain lesions and engages us to avoid confounding factors during the awakening prognostication, which is mainly based on the severity of the EEG. Hence, prognosis should not be decided on an isolated parameter, especially if the dynamic is atypical after a new prescription, even for well-known drugs. For any suspicion, the drug's dosage and replacement should be managed before any premature care's withdrawal.