Acta Neurochir DOI 10.1007/s00701-015-2447-z
LETTER TO THE EDITOR - VASCULAR
Serum Levels of Nimodipine in Enteral and Parenteral Administration in Patients with Aneurysmal Subarachnoid Hemorrhage Tammam Abboud 1 & Jan Regelsberger 1
Received: 27 April 2015 / Accepted: 5 May 2015 # Springer-Verlag Wien 2015
Dear Editor, We would like to thank the colleague, Mr. Tomasz Tykocki, who, from our point of view, has written a very thoughtful comment regarding our article BSerum levels of nimodipine in enteral and parenteral administration in patients with aneurysmal subarachnoid hemorrhage^, and we greatly appreciate the opportunity to respond to his comments. We reported the clinical outcome of our patient cohort in the first submitted version of our manuscript using the modified Rankin scale (mRS) 6 months after discharge. Seven of 15 patients had a good clinical outcome with mRS 1–2. Moderate disability was seen in three patients (mRS 3–4). Five patients died, three of whom suffered devastating cerebral vasospasms with fatal outcome within 2 weeks after hemorrhage. No association was found between low serum concentrations and worse clinical outcome. We removed the clinical outcome from the results section, taking into consideration that the primary focus of our study was on nimodipine serum concentrations and their correlation to the route of nimodipine administration and that we did not perform perfusion scanning (such as CT perfusion) on a routine basis to detect delayed cerebral ischemia. Another point is that, due to the small number of patients included in our study, the correlation between nimodipine serum levels and clinical outcome, if there were any, would not be statistically significant. Therefore, and in light of the studies published by Kronvall et al. and Soppi et al., in which the incidence of delayed ischemic neurologic deficits, number of new ischemic lesions
* Tammam Abboud [email protected] 1
Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
and clinical outcome did not differ between patients who received enteral nimodipine and those who received parenteral nimodipine after subarachnoid hemorrhage [1, 2], we believe that a prospective study with a primary focus on detecting delayed cerebral ischemia and clinical outcome in correlation with the nimodipine serum concentration will be necessary to answer the question of whether lower nimodipine serum concentrations correlate with a higher rate of delayed cerebral ischemia and/or worse clinical outcome. Regarding the issue of how the results of our study could be transferred to daily practice, we would like to point out that one objective of our study was to determine whether the disturbance of gastrointestinal uptake during the first week after hemorrhage, which was found by Soppi et al. [3], persists during the second week. The analysis of nimodipine serum concentrations showed negligible values during enteral administration of nimodipine in two of our patients, both of whom had a high-grade subarachnoid hemorrhage and received nimodipine through a nasogastric tube [4]. From our point of view, this indicates that the disturbance in the gastrointestinal uptake in patients with subarachnoid hemorrhage can clearly persist in the second week after hemorrhage in the subgroup of patients with high-grade hemorrhage who are not able to swallow. Although the therapeutic level of nimodipine in patients with subarachnoid hemorrhage has not yet been determined [5], our results suggest that oral administration of nimodipine in conscious patients during the second week after hemorrhage may lead to sufficient serum concentrations [4]. Accordingly, in our clinical practice, all patients with aneurysmal subarachnoid hemorrhage receive intravenous nimodipine during the first 7 days after hemorrhage. Starting from day 8, we switch to oral nimodipine when the patient is able to swallow. Otherwise, the treatment is continued with intravenous nimodipine.
Acta Neurochir Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
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References 5. 1.
Kronvall E, Undren P, Romner B, Saveland H, Cronqvist M, Nilsson OG (2009) Nimodipine in aneurysmal subarachnoid hemorrhage: a randomized study of intravenous or peroral administration. J Neurosurg 110:58–63
Soppi V, Karamanakos PN, Koivisto T, Kurki MI, Vanninen R, Jaaskelainen JE, Rinne J (2012) A randomized outcome study of enteral versus intravenous nimodipine in 171 patients after acute aneurysmal subarachnoid hemorrhage. World Neurosurg 78:101– 109 Soppi V, Kokki H, Koivisto T, Lehtonen M, Helin-Tanninen M, Lehtola S, Rinne J (2007) Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage—a pilot study. Eur J Clin Pharmacol 63:355–361 Abboud T, Andresen H, Koeppen J, Czorlich P, Duehrsen L, Stenzig J, Westphal M, Regelsberger J (2015) Serum levels of nimodipine in enteral and parenteral administration in patients with aneurysmal subarachnoid hemorrhage. Acta Neurochir 157:763–767 Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P, Sinar J, Bailey S, Skene A (1989) Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298:636–642
LETTER TO THE EDITOR - VASCULAR
Serum Levels of Nimodipine in Enteral and Parenteral Administration in Patients with Aneurysmal Subarachnoid Hemorrhage Tammam Abboud 1 & Jan Regelsberger 1
Received: 27 April 2015 / Accepted: 5 May 2015 # Springer-Verlag Wien 2015
Dear Editor, We would like to thank the colleague, Mr. Tomasz Tykocki, who, from our point of view, has written a very thoughtful comment regarding our article BSerum levels of nimodipine in enteral and parenteral administration in patients with aneurysmal subarachnoid hemorrhage^, and we greatly appreciate the opportunity to respond to his comments. We reported the clinical outcome of our patient cohort in the first submitted version of our manuscript using the modified Rankin scale (mRS) 6 months after discharge. Seven of 15 patients had a good clinical outcome with mRS 1–2. Moderate disability was seen in three patients (mRS 3–4). Five patients died, three of whom suffered devastating cerebral vasospasms with fatal outcome within 2 weeks after hemorrhage. No association was found between low serum concentrations and worse clinical outcome. We removed the clinical outcome from the results section, taking into consideration that the primary focus of our study was on nimodipine serum concentrations and their correlation to the route of nimodipine administration and that we did not perform perfusion scanning (such as CT perfusion) on a routine basis to detect delayed cerebral ischemia. Another point is that, due to the small number of patients included in our study, the correlation between nimodipine serum levels and clinical outcome, if there were any, would not be statistically significant. Therefore, and in light of the studies published by Kronvall et al. and Soppi et al., in which the incidence of delayed ischemic neurologic deficits, number of new ischemic lesions
* Tammam Abboud [email protected] 1
Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
and clinical outcome did not differ between patients who received enteral nimodipine and those who received parenteral nimodipine after subarachnoid hemorrhage [1, 2], we believe that a prospective study with a primary focus on detecting delayed cerebral ischemia and clinical outcome in correlation with the nimodipine serum concentration will be necessary to answer the question of whether lower nimodipine serum concentrations correlate with a higher rate of delayed cerebral ischemia and/or worse clinical outcome. Regarding the issue of how the results of our study could be transferred to daily practice, we would like to point out that one objective of our study was to determine whether the disturbance of gastrointestinal uptake during the first week after hemorrhage, which was found by Soppi et al. [3], persists during the second week. The analysis of nimodipine serum concentrations showed negligible values during enteral administration of nimodipine in two of our patients, both of whom had a high-grade subarachnoid hemorrhage and received nimodipine through a nasogastric tube [4]. From our point of view, this indicates that the disturbance in the gastrointestinal uptake in patients with subarachnoid hemorrhage can clearly persist in the second week after hemorrhage in the subgroup of patients with high-grade hemorrhage who are not able to swallow. Although the therapeutic level of nimodipine in patients with subarachnoid hemorrhage has not yet been determined [5], our results suggest that oral administration of nimodipine in conscious patients during the second week after hemorrhage may lead to sufficient serum concentrations [4]. Accordingly, in our clinical practice, all patients with aneurysmal subarachnoid hemorrhage receive intravenous nimodipine during the first 7 days after hemorrhage. Starting from day 8, we switch to oral nimodipine when the patient is able to swallow. Otherwise, the treatment is continued with intravenous nimodipine.
Acta Neurochir Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
2.
3.
4.
References 5. 1.
Kronvall E, Undren P, Romner B, Saveland H, Cronqvist M, Nilsson OG (2009) Nimodipine in aneurysmal subarachnoid hemorrhage: a randomized study of intravenous or peroral administration. J Neurosurg 110:58–63
Soppi V, Karamanakos PN, Koivisto T, Kurki MI, Vanninen R, Jaaskelainen JE, Rinne J (2012) A randomized outcome study of enteral versus intravenous nimodipine in 171 patients after acute aneurysmal subarachnoid hemorrhage. World Neurosurg 78:101– 109 Soppi V, Kokki H, Koivisto T, Lehtonen M, Helin-Tanninen M, Lehtola S, Rinne J (2007) Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage—a pilot study. Eur J Clin Pharmacol 63:355–361 Abboud T, Andresen H, Koeppen J, Czorlich P, Duehrsen L, Stenzig J, Westphal M, Regelsberger J (2015) Serum levels of nimodipine in enteral and parenteral administration in patients with aneurysmal subarachnoid hemorrhage. Acta Neurochir 157:763–767 Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P, Sinar J, Bailey S, Skene A (1989) Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298:636–642
