Intra-arterial Nimodipine and intra-venous Milrinone for management of delayed cerebral ischemia following aneurysmal subarachnoid haemorrhage

CASE PRESENTATION

• Delayed cerebral ischemia (DCI) is one of the commonest causes of mortality and morbidity in patients with aneurysmal subarachnoid haemorrhage (SAH).
• Various forms of chemical angioplasty protocols are being practiced as a part of care in DCI.
• In the current study, two established chemical angioplasty protocols [intra-arterial nimodipine (IAN) and intra-venous milrinone (IVM)] were compared in terms of clinical improvement and appearance of new cerebral infarcts.

METHODS

• Prospective observational study
• Adult aneurysmal subarachnoid haemorrhage patients admitted between July 2020 and June 2021
• Patients who received either IAN or IVM were included 
• Patients who received both IAN and IVM and/ or who underwent mechanical angioplasty were excluded.

IAN PROTOCOL

• The drug was injected daily in the involved cervical carotid or vertebral artery
• In the angiosuite
• 3mg (15 ml) diluted with normal saline (NS) to 50ml
• Infused over 30min
• For 5-7 days

IVM PROTOCOL

• The drug was given as a continuous intravenous infusion
• 10 ml diluted with NS to 50ml
• started at 7ml/hr, with titration according to clinical status, maximum 15 ml/hour
• For 5-7 days
• In the ICU.

OUTCOMES AT THE END OF THERAPY

• Clinical improvement: improvement in GSC by at least 2 points
• CT/MRI: development of new infarcts
• Statistical analysis: Chi-square test is used

RESULTS

• Thirty-four patients fulfilled inclusion criteria [13/34(38.2%) IVM, 21/34(61.7%) IAN].

GCS AT PRESENTATION

• Patients in the IVM group(vs IAN group) had poorer median GCS (12 vs13).

MOTOR RESPONSE AT PRESENTATION

• Patients in IVM group(vs IAN group) had poorer motor response[<M6 response,5/13(38.4%)vs5/21(23.8%),p=0.36]

   

MODIFIED FISHER GRADES OF SAH AT PRESENTATION

• Patients in IVM group(vs IAN group) had higher grades [modified Fisher ≥3) of SAH {12/13(92.3%)vs8/21(85.7%),p=0.56}].

   

CLINICAL IMPROVEMENT

• After the end of the therapy, more patients in the IAN group(vs IVM group) showed clinical improvement [17/21(80.9%)vs10/13(76.9%),p=0.77].

   

DEVELOPMENT OF NEW INFARCTS

• After the end of the therapy, more patients in the IAN group(vs IVM group) showed the development of new infarcts[15/21(71.4%)vs7/13(53.8%),p=0.29] on the last CT/MRI.

   

DISCHARGED TO HOME

• After the end of the therapy, more patients in the IAN group(vs IVM group) were discharged to home[13/21(61.9%)vs6/13(46.1%),p=0.36]

   

MORTALITIES AT DISCHARGE

• After the end of the therapy, patients in IAN group(vs IVM group) had less mortalities[2/21(9.5%)vs3/13(23.0%),p=0.027].

   

LIMITATIONS

• Single-center study
• Small sample size
• Different routes for administration hence different pharmacokinetics of the both the drugs
• Selection bias- poorer initial GCS and higher SAH grades in Milrinone group at presentation

CONCLUSION

• In this single-center study, Intra-arterial nimodipine proved to be marginally better than intravenous milrinone for management of delayed cerebral ischemia following aneurysmal subarachnoid haemorrhage.