Headache is a common symptom in the Neuroscience Intensive Care Unit (NeuroICU). Our goal is to provide an overview of approaches to headache management for common neurocritical care conditions.

Headache disorders afflict nearly half of patients admitted to the NICU. Commonly encountered disorders featuring headache include cerebrovascular disease, trauma, and intracranial infection. Approaches to pain are highly variable, and multimodal pain regimens are commonly employed. The overall body of evidence supporting therapeutic strategies to manage headache in the critical care setting is slim, and pain control remains suboptimal in many cases with persistent reliance on opioids. Headache is a complex, frequently occurring phenomenon in the NeuroICU care setting. At present, literature on evidence-based practice for management of headache in the critical care setting remains scarce, and despite multimodal approaches, reliance on opioids is commonplace.

Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury.

To assess the effects of indomethacin for adults with severe traumatic brain injury.

We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field.

Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery.

Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods.

We identified no eligible studies for this review, either completed or ongoing.

We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

Headache disorders attributed to low and high intracranial pressure are commonly encountered in specialty headache practices and may occur more frequently than realized. While the headaches resulting from intracranial pressure disorders have what are conventionally thought of as defining characteristics, a substantial minority of patients do not manifest the "typical" features. Moreover, patients with intracranial pressure disorders may also have a preexisting primary headache disorder. Heightening the complexity of the presentation, the headaches of intracranial pressure disorders can resemble the phenotype of a primary disorder. Lastly, patients with so-called intracranial "hypotension" often have normal CSF pressure and neuroimaging studies. Thus, a high index of suspicion is needed. The published literature has inherent bias as many types of specialists evaluate and treat these conditions. This article reviews the key points to emphasize the history, examination, and laboratory evaluation of patients with intracranial pressure disorders from a neurologist's perspective.

Lumbar puncture opening pressure in patients with spontaneous intracranial hypotension was low enough to meet diagnostic criteria (≤60 mm CSF) in only 34% of patients in one study. Most patients had an opening pressure in the low normal to normal range, and 5% had an opening pressure of 200 mm CSF or more. Diskogenic microspurs are a common cause of this syndrome. The Idiopathic Intracranial Hypertension Treatment Trial found that most participants had a headache phenotype resembling migraine or tension-type headache. No "typical" or characteristic headache phenotype was found, and headache-related disability was severe at baseline. Headache disability did not correlate with the lumbar puncture opening pressure at baseline or at the 6-month primary outcome period. Although participants who were randomly assigned to acetazolamide had a lower mean CSF opening pressure at 6 months, headache disability in that group was similar to the group who received placebo.

Significant overlap is seen in the symptoms of high and low CSF pressure disorders and in those of primary headache disorders. Neurologists are frequently challenged by patients with headaches who lack the typical clinical signs or imaging features of the pseudotumor cerebri syndrome or spontaneous intracranial hypotension. Even when characteristic symptoms and signs are initially present, the typical features of both syndromes tend to lessen or resolve over time; consider these diagnoses in patients with long-standing "chronic migraine" who do not improve with conventional headache treatment. While the diagnostic criteria for pseudotumor cerebri syndrome accurately identify most patients with the disorder, at least 25% of patients with spontaneous intracranial hypotension have normal imaging and over half have a normal lumbar puncture opening pressure. Detailed history taking will often give clues that suggest a CSF pressure disorder. That said, misdiagnosis can lead to significant patient morbidity and inappropriate therapy.

Objectives: Standard management strategies for lowering intracranial pressure (ICP) in traumatic brain injury has been well-studied, but the use of lesser known interventions for ICP in subarachnoid hemorrhage (SAH) remains elusive. Searches were performed in PubMed and EBSCO Host to identify best available evidence for evaluation and management of medically refractory ICP in SAH. The role of standard management strategies such as head elevation, hyperventilation, mannitol and hypertonic saline as well as lesser known management such as sodium bicarbonate, indomethacin, tromethamine, decompressive craniectomy, decompressive laparotomy, hypothermia, and barbiturate coma are reviewed. We also included dose concentrations, dose frequency, infusion volume, and infusion rate for these lesser known strategies. Nonetheless, there is still a gap in the evidence to recommend optimal dosing, timing and its role in the improvement of outcomes but early diagnosis and appropriate management reduce adverse outcomes.

Monitoring intracranial pressure in comatose patients with severe traumatic brain injury (TBI) is considered necessary by most experts. Acute intracranial hypertension (IHT), when severe and sustained, is a life-threatening complication that demands emergency treatment. Yet, secondary anoxic-ischemic injury after brain trauma can occur in the absence of IHT. In such cases, adding other monitoring modalities can alert clinicians when the patient is in a state of energy failure. This article reviews the mechanisms, diagnosis, and treatment of IHT and brain hypoxia after TBI, emphasizing the need to develop a physiologically integrative approach to the management of these complex situations.

Successful use of i.v. indomethacin for urgent management of elevated intracranial pressure (ICP) due to acute liver failure is reported.

A 42-year-old woman receiving intensive care for fulminant hepatic failure secondary to acetaminophen toxicity developed cerebral edema and intracranial hypertension refractory to standard pharmacotherapy and respiratory support measures. A computed tomography (CT) scan of the patient's head was ordered as part of an evaluation for liver transplantation, but the patient's severely elevated ICP precluded supine positioning for the CT study (throughout the hospital stay, the head of the patient's bed was kept at a 30° angle to optimize cerebral venous outflow). With administration of indomethacin 10 mg by i.v. injection, the ICP decreased from 29 to 13 mm Hg and remained at goal after the patient was placed in a fully supine position for a period long enough to permit the CT scan. Indomethacin was used a second time to facilitate CT imaging several days later. No adverse effects attributable to indomethacin use were documented. Although the patient underwent successful liver transplantation, her mental status and overall clinical status continued to deteriorate and she died on postoperative day 12.

Despite the poor overall patient outcome in this case, i.v. indomethacin was successfully used to decrease ICP in order to facilitate CT imaging as part of a transplantation eligibility workup.

The burden of disease and so the need for care is often greater at hospitals in emerging economies. This is compounded by frequent restrictions in the delivery of good quality clinical care due to resource limitations. However, there is substantial heterogeneity in this economically defined group, such that advanced brain monitoring is routinely practiced at certain centers that have an interest in neurocritical care. It also must be recognized that significant heterogeneity in the delivery of neurocritical care exists even within individual high-income countries (HICs), determined by costs and level of interest. Direct comparisons of data between HICs and the group of low- and middle-income countries (LAMICs) are made difficult by differences in patient demographics, selection for ICU admission, therapies administered, and outcome assessment. Evidence suggests that potential benefits of multimodality monitoring depend on an appropriate environment and clinical expertise. There is no evidence to suggest that patients in LAMICs where such resources exist should be treated any differently to patients from HICs. The potential for outcome benefits in LAMICs is arguably greater in absolute terms because of the large burden of disease; however, the relative cost/benefit ratio of such monitoring in this setting must be viewed in context of the overall priorities in delivering health care at individual institutions.

Refractory intracranial hypertension (RICH) is associated with high mortality in severe traumatic brain injury (sTBI). Indomethacin (INDO) can decrease intracranial cerebral pressure (ICP) improving cerebral pressure perfusion (CPP). Our aim was to determine modifications in ICP and CPP following INDO in RICH secondary to sTBI.

INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by continuous 2-h infusion period (0.5 mg/kg/h). Clinical outcome was assessed at 30 days according to Glasgow Outcome Scale (GOS). Differences in ICP and CPP values were assessed using repeated-measures ANOVA. Receiver operating characteristic curve (AUC) was used for discrimination in predicting 30-day survival and good functional outcome (GOS 4 or 5). Analysis of INDO safety profile was also conducted.

Thirty-two patients were included. Median GCS score was 6 (interquartile range: 4-7). The most frequent CT finding was the evacuated mass lesion (EML) according to Marshall classification (28.1 %). Mortality rate was 34.4 %. Within 15 min of INDO infusion, ICP decreased (Δ%: -54.6 %; P < 0.0001), CPP increased (Δ%: +44.0 %; P < 0.0001), and the remaining was stable during the entire infusion period. Patients with good outcome (n = 12) showed a greater increase of CPP during INDO test (P = 0.028). CPP response to INDO test discriminated moderately well surviving patients (AUC = 0.751; P = 0.0098) and those with good functional recovery (AUC = 0.763; P = 0.0035) from those who died and from those with worse functional outcome, respectively. No adverse events were observed.

INDO appears effective in reducing ICP and improving CPP in RICH. INDO test could be a useful tool in identifying RICH patients with favorable outcome. Future studies are needed.