Management of pain after aneurysmal subarachnoid hemorrhage is challenging due to risks of complications from uncontrolled pain. NSAIDs and acetaminophen are first-line treatments due to safety, though opioids may be needed. Adjunctive treatments include short courses of corticosteroids and anticonvulsants like gabapentin or pregabalin. Careful pain management is crucial to prevent issues such as re-rupture or hypertension, while mitigating side effects from treatments.

1. MANAGEMENT OF PAIN AFTER
ANEURYSMAL SUBARACHNOID
HEMORRHAGE
Ade Wijaya, MD – April
2020

2. INTRODUCTION
• Aneurysmal subarachnoid hemorrhage (SAH): life threatening
• Multidisciplinary Approach
• Often experience tremendous pain and discomfort
Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263–306.
Etminan N, Brown RD, Beseoglu K, Juvela S, Raymond J, Morita A, et al. The unruptured intracranial aneurysm treatment score. Neurology 2015;85:881–9.
Glisic EK, Gardiner L, Josti L, Dermanelian E, Ridel S, Dziodzio J, et al. Inadequacy of headache management after subarachnoid hemorrhage. Am J Crit Care 2016;25:136–43.

3. COMPLICATION OF UNDERTREATED
PAIN
Uncontrolled pain in SAH patients can contribute to many serious
complications including:
 Aneurysm re-rupture
 Pain-induced hypertension
 Complications due to prolonged immobility
Basali A, Mascha EJ, Kalfas I, Schubert A. Relation between perioperative hypertension and intracranial hemorrhage after craniotomy. Anesthesiology 2000;93:48–54.
Mordhorst C, Latz B, Kerz T, Wisser G, Schmidt A, Schneider A, et al. Prospective assessment of postoperative pain after craniotomy. J Neurosurg Anesthesiol 2010;22:202–6.

4. PATHOPHYSIOLOGY

5. NSAIDS
• NSAIDs are non-selective, reversible inhibitors of cyclooxygenase 1
and 2 (COX-1/2) and exert their analgesic and antipyretic effects
through the reduction of acute phase reactants and downstream pro-
inflammatory cytokines such as prostaglandins. They work to reduce
pain from meningeal irritation and arachnoiditis.
•In general, their use in neurosurgical patients is limited due to their
effects on bleeding and blood pressure. NSAIDs have also been
shown to reduce renal blood flow and increase the risk of
gastrointestinal ulcer formation.
• In patients with secured aneurysms, NSAIDs may actually be
neuroprotective and anti-inflammatory.
Rasouli J, Watson C, Yaeger K, Ladner T, Kellner C, Dangayach NS. Pain control after aneurysmal subarachnoid hemorrhage: A contemporary literature review. Journal of Clinical Neuroscience. 2019 Oct 1;68:9-12.

6. CORTICOSTEROIDS
• Dexamethasone inhibits phospholipase A2, which is a main
upstream inflammatory enzyme that is upregulated after SAH
• It is used sparingly as it has been associated with poorer outcomes
and a possible increased risk of vasospasm. These effects, in addition
to common side-effects such as hyperglycemia, agitation, and
immune suppression preclude its routine use
• Relatively safe and mildly effective if used for a short period of time
(<7 days)
Rasouli J, Watson C, Yaeger K, Ladner T, Kellner C, Dangayach NS. Pain control after aneurysmal subarachnoid hemorrhage: A contemporary literature review. Journal of Clinical Neuroscience. 2019 Oct 1;68:9-12.

7. ANTICONVULSANTS
• Gabapentin and pregabalin may be useful adjuncts in the treatment
of SAH headache
• Dose: maximum: 2700 mg/day; median: 1200 mg/day with minimal
side-effect
• Avoid use in patients with a history of opioid abuse or substance use
disorders
Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol 2017;27:1185–215.
Dhakal LP, Hodge DO, Nagal J, Mayes M, Richie A, Ng LK, et al. Safety and tolerability of gabapentin for aneurysmal subarachnoid hemorrhage (SAH) headache and meningismus. Neurocrit Care 2015;22:414–21.

8. ACETAMINOPHEN
• Acetaminophen exerts its analgesic effects by inhibiting COX-1 and
COX-2. Recent studies suggest its effects on the central nervous
system are secondary to COX-3 inhibition.
• Well tolerated, does not cause sedation, is a potent anti-pyretic, has
no effects on platelet function, and may possess anti-inflammatory
properties.
• Dosages up to 4 g/day (oral = intravenous).
• While acetaminophen alone may not achieve adequate analgesia in
SAH patients; it should be considered to be an essential component
of the pain management protocol for SAH patients.
Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther 2005;12:46–55.
Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus oral acetaminophen for pain: systematic review of current evidence to support clinical decision-making. Can J Hosp Pharm 2015;68:238–47.
Muroi C, Hugelshofer M, Seule M, Keller E. The impact of nonsteroidal anti-inflammatory drugs on inflammatory response after aneurysmal subarachnoid hemorrhage. Neurocrit Care 2014;20:240–6.
Swope R, Glover K, Gokun Y, Fraser JF, Cook AM. Evaluation of headache severity after aneurysmal subarachnoid hemorrhage. Interdiscip Neurosurg 2014;1:119–22.

9. OPIOIDS
• Oral or intravenous opioid medications remain the primary treatment
for SAH headache.
• In the CNS, opioids also affect mental status and respiratory drive,
via the augmentation of GABA-ergic neurotransmission. Therefore,
side effects of opioid analgesia are of particular concern in SAH
patients when a reliable neurologic exam is essential to identify
delayed cerebral injury due to vasospasm or hydrocephalus.
Zhang X, Bao L, Li S. Opioid receptor trafficking and interaction in nociceptors. Br J Pharmacol 2015;172:364–74.

10. SUMMARY
 The treatment of SAH headache is challenging, complex, and highly
refractory to standard pain medications.
 NSAIDs and COX-II inhibitors are moderately effective and safe to
administer for secured aneurysm in the absence of intraparenchymal
hematoma or active hemorrhage.
 Acetaminophen should be given to all patients without liver dysfunction or
acetaminophen allergy.
 Anticonvulsants such as pregabalin or gabapentin can be useful adjuncts
 A short low-dose dexamethasone taper (<7 days) is an option for patients
who have headaches refractory to all the above medications
 We do not recommend opioids due to the risk of dependence, withdrawal,
and rebound headaches

11. THANK YOU