Vasopressin Continuous Infusion Improves Intracranial Pressure and Patient Outcomes after Surgical Clipping or Endovascular Coiling of Cerebral Aneurysm.

BACKGROUND: Hypertensive therapy prevents vasospasm-related delayed ischemic neurologic deficit and infarcts. New alternatives would include vasopressin which has vasoconstrictive effects and positive influence on cerebral perfusion pressure (CPP) and intracranial pressure (ICP). AIMS: The aim of this study is to demonstrate the value of vasopressin intravenous infusion (IVI) in decreasing ICP and preventing vasospasm following surgical clipping or endovascular coiling. SETTINGS AND
DESIGN: A triple-blind prospective randomized controlled study. SUBJECTS AND METHODS: Thirty patients, 25-60 years, both genders, had undergone surgical clipping or endovascular coiling for a cerebral aneurysm, World Federation of Neurosurgical Societies (WFNS) grade 1-3 (15 patients in each); Group I (Vasopressin): 0.1-0.4 unit/min and Group II (Norepinephrine): 5-20 ug/min with target systolic blood pressure 160-180 mmHg. STATISTICAL ANALYSIS: SPSS version 25 software was used for analysis.
RESULTS: Invasive mean arterial pressure (MAP) showed the insignificant difference between the two groups, but ICP showed a significant decrease in Group V from hour 24 to 168 hence calculated CPP showed a significant increase in Group V at most times from hour 36 to 168. Glasgow Coma Scale showed a significant decrease in Group N from hour 138 due to the occurrence of vasospasm. The incidence of vasospasm, mechanical ventilation, and 28-day mortality were significantly lower in Group V with 81% risk reduction of vasospasm and better survival.
CONCLUSION: Vasopressin IVI improved ICP, MAP, CPP and patient outcomes safely by reducing the incidence of cerebral vasospasm, and 28-day mortality after clipping or coiling of the cerebral aneurysm. Copyright:

INTRODUCTION

What is generally known that surgical clipping and endovascular coiling are the treatment of choice for cerebral aneurysm.[1] Although the pathophysiology of cerebral vasospasm is not totally understood but once developed: vascular diameter decreases, vascular resistance increases, and cerebral blood flow (CBF) decreases. This is followed by delayed ischemic neurological deficit in 17%–40% of cases; half of which results in cerebral infarction.[2]

Transcranial Doppler (TCD) is a novel noninvasive modality for screening patients at risk of vasospasm by measuring mean flow velocity (MFV) and it is superior to angiography in availability, price, and usability.[3]

Arginine-vasopressin (AVP) demonstrated different mechanisms of actions by reciprocation of different actions and receptors. The mechanism of vasoconstriction is primarily by the AVPR1α, a G-protein coupled receptor which is considered the main effector on the smooth muscle of vessels, platelets, and hepatocytes); it stimulates a phosphatidylinositol-calcium signal pathway leading to smooth muscle contraction. The mechanism of vasodilation AVP is possibly due to nitric oxide synthesis (a potent vasodilator of cerebral and coronary vessels) and stimulation of receptors of oxytocin.[4] Those different mechanisms make AVP a potentially useful drug for neurosurgical patients.[5]

This study is the first to utilize vasopressin intravenous infusion (IVI) while measuring not only the mean arterial blood pressure (MAP) and the cerebral perfusion pressure (CPP) but also the intracranial pressure (ICP) and the clinical outcomes on the participants.

Aim of the study

The aim of this study is to demonstrate the value of vasopressin IVI in decreasing ICP and preventing vasospasm following surgical clipping or endovascular coiling.

SUBJECTS AND METHODS

This triple-blind, prospective, randomized, controlled study was conducted from November 2016 to October 2018. All data of patients were kept confidential using a secret code and a private file for each patient. After protocol approval by the ethical committee, written informed consent was obtained from each patient or relative. Each patient was informed and received an elaborate explanation about the purposes of the study, the risks involved and their rights to withdraw and/or end participation at any time.

Thirty participants were included using the following inclusion criteria: ages between 25 and 60 years, all genders, had undergone surgical clipping or endovascular coiling for a cerebral aneurysm within 24 h of subarachnoid hemorrhage diagnosis, if occurred, and World Federation of Neurosurgical Societies (WFNS)[6] grade 1–3 [Table 1] (i.e., Glasgow Coma Scale [GCS] 13–15). Exclusion criteria were: vasospasm (diagnosed by TCD or CT angiography) before the start of IVI, WFNS grade 4 or 5 (GCS 6–12), prior cognitive dysfunction, peripheral vascular disease, and disorders such as cardiac, pulmonary, hepatic, renal, neuromuscular, and endocrinal.

Table 1

World Federation of Neurosurgical Societies (WFNS) grading system for aneurysmal subarachnoid hemorrhage

Grade	GCS score	Motor deficit
I	15	Absent
II	13 or 14	Absent
III	13 or 14	Present
IV	7-12	Present or absent
V	3-6	Present or absent

GCS=Glasgow coma scale

Intraoperative management

All patients were under general anesthesia during clipping or coiling. The induction of anesthesia was by fentanyl 2 μg.kg-1, lidocaine 1.5 mg.kg-1, propofol 2 mg.kg-1, and cisatracurium 0.15 mg.kg-1 followed by endotracheal intubation. Maintenance was done with total intravenous anesthesia by (remifentanil 0.05–2 μg/kg/min, propofol 50–200 μg.kg-1.min-1), and cisatracurium infusion of 0.1 mg.kg-1.H-1. A central venous catheter 7F was inserted into the subclavian vein for fluid and drug administration. External ventricular device (EVD) was placed before extubation.[7]

In patients with GCS ≥13, uncomplicated surgery, stable hemodynamics, and temperature >36°C; extubation was performed after the confirmation of spontaneous ventilation, adequate blood gas variables, and other weaning criteria (e.g., Pa/FiO2 >300, PaCO2 35–45 mmHg).

Surgical intensive care unit management

Patients were transferred to surgical intensive care unit and connected to the monitor (ECG, pulse oximetry, invasive arterial blood pressure, temperature, and ICP [EVD was connected to the transducer which was 1 cm above the level of the tempomandibular joint]) and CPP was calculated by the following equation: CPP = MAP − ICP.[8]

All patients were kept normovolemic by the infusion of saline 0.9% 80–100 mL.H-1 (the goal is to maintain CVP 5–8 mmHg).[9]

Group allocation

Computer-Generated randomization was done, and numbers were concealed in sealed envelopes showing the group of the assignment. The study pharmacists prepared infusions of both study drugs (with only labels of grouping) and randomized the cases. Patients (and families) and other research personals were blinded to grouping for the duration of the trial.

Patients were allocated into two groups (15 patients in each); Group I (vasopressin group): Vasopressin continuous infusion 0.1–0.4 unit.min-1 and Group II (Norepinephrine group): Norepinephrine continuous infusion 5–20 μg.min-1 as a control group [Figure 1]. The target was systolic blood pressure (SBP) of 160–180 mmHg and MAP of 90–120 mmHg. Crossover to the other group was not permitted. All patients, authors, and observers were blind to the grouping.

Figure 1

Patient flowchart of the study protocol

Both vasopressin (15 unit) and norepinephrine (7.5 mg) were mixed with 125 ml 5% dextrose in water (0.12 unit.mL-1 vasopressin and 60 μg.mL-1 norepinephrine). Infusion began at 5 mL.H-1 up to 20 mL.H-1 and titrated by increase or decrease 2.5 mL.H-1 every 10 min (i.e., vasopressin 0.01 up to 0.04 unit.min-1, whereas norepinephrine 5 up to 20 μg.min-1).

Occurrence of vasospasm was diagnosed by TCD (MFV >120 cm.s-1). When it occurred, oral (or nasogastric tube) 60 mg nimodipine every 4 h for up to 21 days, Hetastarch (6%) 500 ml bolus infusion added to the basic saline infusion (to maintain CVP 8–12 mmHg) were given. Intracranial hypertension was treated with cerebrospinal drainage by EVD.[10]

Measurements

SBP, MAP, diastolic blood pressure (DBP) (invasive), GCS, ICP, and CPP (calculated) were recorded every 6 h for the next seven successive postoperative days (168 H). Organ functions (serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, creatinine, and blood urea) were done daily (for seven successive days). The occurrence of cerebral vasospasm (by TCD), 28-day mortality was recorded for all patients.

Outcome measures

The primary outcome was ICP reduction and the secondary outcome was CPP, GCS, the incidence of cerebral vasospasm, and 28-day mortality.

Statistical analysis

Minitab® (Version 17.1.0, Minitab, Inc.) software as ICP with norepinephrine infusion was 17.0 ± 1.36 in a previous study,[10] with the assumption that vasopressin may decrease ICP 20% (3.4 mmHg), 0.05 and a power 99%. We added more cases to compensate for the dropped-out cases.

Statistical analysis was performed using SPSS version 25 software (SPSS Inc., Chicago, IL, USA). Normality of data was checked with the Shapiro–Wilks test. Numerical variables were presented as mean and standard deviation and compared between the two groups utilizing Student's independent t-test for data showing normal distribution. If abnormal distribution variables (GCS), they were presented as median and interquartile range and compared using the Mann–Whitney U-test. Categorical variables were presented as patients’ number and percentage (%) and were analyzed utilizing the Chi-square test or Fisher's exact test when appropriate. P <0.05 was considered statistically significant.

RESULTS

In this study, 39 patients were assessed for eligibility; five patients did not meet the inclusion criteria and 4 patients refused to participate in the study. Thirty patients were randomized into two groups 15 patients in each one; vasopressin group and norepinephrine group. All patients were included in the follow-up and analysis [Figure 1].

As regards gender, age, weight, WFNS grading score, and type of operation, there was no significant difference between groups [Table 2]. Furthermore, organ functions showed no significant changes between both groups [Table 3].

Table 2

Demographic data, type of operation, World Federation of Neurological Surgeons grading scale, cerebral vasospasm, mechanical ventilation, and 28-day mortality

	Group V (n=15), n (%)	Group N (n=15), n (%)	P
Age (y)	41.93±7.3	44.33±4.8	0.314†
Weight (kg)	81.67±6.1	79.93±6.3	0.367†
Gender (male)	8 (53.3)	10 (66.7)	0.456‡
Type of operation (clipping/coiling)	6/9	5/10	0.705‡
WFNS grade (I/II/III)	8/5/2	9/4/2	0.919‡
Cerebral vasospasm	1 (6.7)	7 (46.7)	0.035§
Onset of vasospasm (H)	90 (1 case only)	120 (105-132)	-
Mechanical ventilation	1 (6.7)	6 (40)	0.017§
28-day mortality	0	5 (33.3)	0.042§

†By Student’s t-test, ‡By Chi-square, §by Fisher’s Exact. WFNS=World Federation of Neurological Surgeons

Table 3

Organ (liver and kidney) functions

Organ function	Group	Day
		1st	2nd	3rd	4th	5th	6th	7th
Serum ALT (U.L=1)	Group I	37.8±1.8	38.7±4.04	37.6±1.5	36.93±1.03	38.6±1.5	33.13±1.59	37.93±1.03
	Group II	42.1±1.5	40.4±2.13	38.3±2.41	38.6±3.8	38.3±2.41	35.65±1.65	38.6±3.8
	P†	0.58	0.78	0.14	0.48	0.1	0.39	0.48
Serum AST (U.L=1)	Group I	21.5±5.6	23.4±5.34	21.0±4.0	24.2±6.1	22.53±2.7	25.4±4.9	24.07±4.41
	Group II	22.4±4.6	25.0±5.74	23.06±4.26	24±4.7	23.6±4.8	24.7±5.4	24.3±5.8
	P†	0.645	0.436	0.205	0.921	0.459	0.700	0.88
Serum albumin (g.L-1)	Group I	31.66±3.26	30.46±3.13	30.73±3.26	31.20±3.80	32.20±3.00	31.26±2.49	32.06±2.71
	Group II	32.26±2.89	30.93±3.88	31.60±3.60	33.20±2.78	31.80±2.27	30.60±3.92	31.73±2.84
	P†	0.725	0.720	0.495	0.111	0.684	0.583	0.745
Serum bilirubin (mmol.L-1)	Group I	5.73±1.75	6.73±2.18	5.46±2.13	6.33±1.63	5.86±1.92	4.60±2.09	4.46±2.13
	Group II	4.86±2.44	6.13±2.19	6.78±2.45	5.21±2.22	4.92±1.89	4.85±1.79	3.85±1.65
	P†	0.274	0.460	0.133	0.132	0.198	0.726	0.400
Serum urea (mmol.L-1)	Group I	5.7±0.3	4.4±0 0.4	5.53±0.5	4.0±0.4	4.5±0.5	4.7±0.27	6.8±0.4
	Group II	5.61±0.25	4.2±0.3	5.62±0.4	4.4±0.6	4.6±0.4	4.6±0.29	6.8±0.3
	P†	0.379	0.415	0.32	0.16	0.32	0.336	0.96
Serum creatinine (mmol.L-1)	Group I	70.86±5.19	68.80±4.03	74.00±6.95	77.06±6.62	80.40±6.98	79.73±7.07	77.86±8.07
	Group II	70.73±5.83	70.73±5.53	68.13±6.47	75.93±5.64	77.20±6.58	81.80±3.27	78.73±8.19
	P†	1.658	0.108	0.126	0.618	0.101	0.313	0.317

†By Student’s t-test. ALT=Alanine aminotransferase, AST=Aspartate aminotransferase

Invasive SBP, DBP, and MAP showed no significant difference between the two groups [Table 4 and Figure 2]. ICP showed a significant reduction in Group V compared to that of Group N from 24 h to 168 h [Table 5 and Figure 2]. CPP (calculated) showed a significant increase in Group V than that of Group N at most times from 36 h to 168 h [Table 6]. GCS showed a significant decrease in Group N in comparison with Group V from 138 h to 168 h (due to the occurrence of vasospasm) [Table 7].

Table 4

Mean arterial pressure (mmHg) in both groups

Time (h)	Mean±SD		P†
	Group I (n=15)	Group II (n=15)
Baseline	101.4±7.7	100.4±7.4	0.728
6	118.3±5.6	116.9±7.5	0.583
12	123.2±5.3	116.7±6.6	0.007
18	121.3±6.9	121.0±6.6	0.918
24	123.3±5.8	126.3±6.4	0.213
30	122.9±4.8	126.3±5.1	0.083
36	125.2±4.7	123.7±5.2	0.428
42	122.1±5.1	119.9±5.3	0.273
48	122.8±5.7	125.1±5.4	0.296
54	125.2±4.4	125.7±5.0	0.757
60	126.5±4.3	124.9±5.1	0.384
66	128.3±5.2	124.8±5.0	0.079
72	124.3±5.2	120.9±4.5	0.077
78	130.0±5.1	121.5±4.6	<0.001
84	123.2±5.9	123.7±5.0	0.840
90	124.1±3.2	123.0±6.2	0.569
96	125.4±3.6	122.9±5.1	0.156
102	123.2±3.5	120.2±5.4	0.093
108	124.0±4.6	120.3±6.3	0.083
114	124.7±3.8	122.7±4.9	0.240
120	126.1±3.2	125.4±5.4	0.696
126	126.8±4.2	126.1±4.3	0.662
132	126.6±4.3	126.5±4.4	0.979
138	126.5±4.0	127.7±4.8	0.463
144	126.2±3.9	126.6±5.0	0.794
150	126.2±3.9	122.1±5.8	0.033
156	122.8±5.0	119.6±5.3	0.113
162	124.8±4.2	119.5±6.3	0.014
168	126.9±4.3	126.9±5.1	0.99

†By Student’s t-test. SD=Standard deviation

Figure 2

Systolic blood pressure, mean arterial blood pressure, diastolic blood pressure, and intracranial pressure (mmHg) in both groups

Table 5

Intracranial pressure (mmHg) in both groups

	Mean±SD		P†
	Group I (n=15)	Group II (n=15)
Baseline	17.1±1.7	17.3±1.8	0.765
6 h	16.1±1.5	17.1±1.6	0.124
12 h	14.5±1.4	15.1±1.9	0.341
18 h	13.4±1.8	13.9±1.4	0.391
24 h	12.8±1.4	15.5±1.8	<0.001
30 h	13.8±1.6	16.5±1.9	<0.001
36 h	13.2±2.0	15.9±1.8	0.001
42 h	13.7±1.9	16.5±2.0	0.001
48 h	12.2±1.8	14.9±2.0	0.001
54 h	12.5±1.7	15.1±1.8	0.001
60 h	12.2±1.6	14.8±2.2	0.001
66 h	12.7±1.4	15.3±1.8	<0.001
72 h	12.5±1.6	15.1±1.7	<0.001
78 h	12.1±1.9	15.8±2.4	<0.001
84 h	12.5±1.7	14.9±2.1	0.003
90 h	12.4±1.4	14.9±1.8	<0.001
96 h	11.3±2.3	14.8±1.1	<0.001
102 h	11.1±2.0	14.7±2.2	<0.001
108 h	11.1±2.3	14.7±1.8	<0.001
114 h	12.7±2.1	15.5±2.6	0.003
120 h	11.3±3.1	14.9±2.0	0.001
126 h	11.7±2.1	14.9±1.8	<0.001
132 h	12.3±1.8	15.5±1.3	<0.001
138 h	12.9±1.7	15.9±1.5	<0.001
144 h	13.3±1.4	16.1±1.2	<0.001
150 h	12.9±1.7	15.7±1.5	<0.001
156 h	12.4±2.1	15.3±2.0	0.001
162 h	12.9±1.7	15.6±1.5	<0.001
168 h	12.8±1.9	15.6±1.7	<0.001

†By Student’s t-test. SD=Standard deviation

Table 6

Cerebral perfusion pressure (mmHg) in both groups

	Mean±SD		P†
	Group I (n=15)	Group II (n=15)
Baseline	84.3±8.0	83.1±7.8	0.692
6 h	102.2±6.1	99.9±7.2	0.366
12 h	108.8±6.0	101.6±6.4	0.005
18 h	107.9±7.6	107.1±6.7	0.769
24 h	110.5±6.0	110.7±6.8	0.927
30 h	109.1±5.2	109.7±4.8	0.746
36 h	112.0±5.2	107.7±5.6	0.046
42 h	108.4±5.3	103.5±5.0	0.017
48 h	110.6±5.6	110.2±5.7	0.844
54 h	112.7±5.1	110.7±5.6	0.322
60 h	114.3±3.9	110.1±4.8	0.018
66 h	115.6±5.6	109.5±5.3	0.006
72 h	111.8±6.0	105.9±5.0	0.008
78 h	117.9±5.9	105.7±5.7	<0.001
84 h	110.8±5.9	108.8±5.6	0.368
90 h	111.7±3.5	108.1±5.7	0.056
96 h	114.1±2.9	108.1±4.9	0.001
102 h	112.1±3.9	105.5±5.7	0.001
108 h	112.9±4.9	105.6±6.8	0.003
114 h	112.1±3.9	107.2±5.2	0.009
120 h	114.7±3.0	110.5±4.9	0.010
126 h	115.0±5.3	111.1±4.6	0.047
132 h	114.3±4.8	111.0±4.6	0.074
138 h	113.6±4.8	111.9±4.7	0.356
144 h	112.8±4.4	110.5±5.0	0.211
150 h	113.3±4.5	106.3±5.9	0.001
156 h	110.4±5.9	104.3±5.9	0.011
162 h	111.9±5.3	103.9±5.9	0.001
168 h	114.1±5.3	111.3±5.6	0.186

†By Student’s t-test. SD=Standard deviation

Table 7

Glasgow coma scale in both groups

	Group I (n=15)		Group II (n=15)		P‡
	Median	IQR	Median	IQR
Baseline	15	14-15	15	14-15	0.807
6 h	15	14-15	15	14-15	0.807
12 h	15	14-15	15	14-15	0.807
18 h	15	14-15	15	14-15	0.807
24 h	15	14-15	15	14-15	0.807
30 h	15	14-15	15	14-15	0.807
36 h	15	14-15	15	14-15	0.794
42 h	15	14-15	15	14-15	0.571
48 h	15	14-15	15	14-15	0.571
54 h	15	14-15	15	14-15	0.571
60 h	15	14-15	15	14-15	0.391
66 h	15	14-15	15	14-15	0.391
72 h	15	14-15	15	14-15	0.391
78 h	15	14-15	15	14-15	0.391
84 h	15	14-15	15	14-15	0.571
90 h	15	14-15	15	14-15	0.500
96 h	15	14.5-15	15	14-15	0.653
102 h	15	14.5-15	15	13.5-15	0.372
108 h	15	14.5-15	15	13.5-15	0.211
114 h	15	14.5-15	15	13.5-15	0.211
120 h	15	14.5-15	15	12-15	0.167
126 h	15	14.5-15	14	8-15	0.082
132 h	15	14.5-15	14	8.5-15	0.087
138 h	15	14.5-15	14	6-15	0.027
144 h	15	14.5-15	14	5.5-15	0.028
150 h	15	14.5-15	14	5-15	0.011
156 h	15	14.5-15	14	5.5-15	0.013
162 h	15	14.5-15	14	6.5-15	0.017
168 h	15	14.5-15	12	5.5-14.5	0.004

IQR: Interquartile range, ‡By Mann-Whitney test

As regard the incidence of cerebral vasospasm, mechanical ventilation, and 28-day mortality, there was a significant decrease in Group V than that of Group N [Table 2]. There was 81% risk reduction in Group V than Group N with 95% confidence interval [CI] (0.03–1.26). The Kaplan–Meier survival analysis curve showed better survival with Group V with hazards ratio 5.89 times in Group N compared to Group V with 95% CI (1.18–29.35) [Figure 3].

Figure 3

Kaplan–Meier survival analysis curve for mortality in both groups

DISCUSSION

In the present study, we introduced a novel therapy by a vasopressin infusion in cerebral aneurysm patients from the early stage through the risk period for vasospasm postclipping or endovascular coiling.

Invasive MAP was comparable between the two groups, but ICP showed a significant decrease in Group V in comparison with Group N from 24 h to 168 h, so CPP showed a significant increase in Group V than that of Group N at most times from 36 h to 168 h [Table 6].

These co-linked results are dependent on each other and cannot be explained separately but by the combined effects of vasopressin as a potent VC effect in addition to the positive inotropic effect which increase the MAP and decrease ICP and subsequently increased the CPP, in Group V compared to Group N. These results are supported by the findings of Dudkiewicz and Proctor in 2008[11] who could demonstrate that AVP maintained CPP and improved ICP with increased cerebral tissue oxygenation better than phenylephrine.

These encouraging results enable us to consider AVP is a safe and effective alternative vasopressor to norepinephrine in neurosurgical patients, especially after SAH, giving the desired results of an increased MAP, CPP, and decreased ICP. However we cannot ignore the query of Bele et al.[12] about AVPR1α-mediated contraction of smooth muscle cells that appears to happen also in cerebral vessels, reflected by the decrease in CBF after AVP administration and in contrary, norepinephrine increases MAP without a change in cerebral vessels, and hence, they said that norepinephrine is the ideal catecholamine for SAH. As an answer to their query, we suggested that the influence of vasopressin on oxytocin receptors leading to vasodilation and also, after rigorous research authors found an explanation in a research done by Van Haren et al.;[5] they stated that the AVPR1a activation leads to an elevation in MAP and decrease in ICP due to small cerebral vasoconstriction.

With all such analysis and results obtained from the present study, a couple of asking questions appeared: First is vasopressin constrictor or dilator for small cerebral vessels and second is increase the MAP and decrease ICP and subsequently increased the CPP enough for prophylaxis against cerebral vasospasm and improved patients’ outcomes postclipping or endovascular coiling during the period of maximum vasospasm incidence (between the 4th and 11th day). Our results clearly revealed that increased CPP (by increased MAP and decreased ICP) without a concomitant improvement of CBF. This was apparent in patients with increased TCD velocities suggestive of cerebral vasospasm.

As regards the incidence of cerebral vasospasm, mechanical ventilation, and 28-day mortality, there was significant decrease in Group V than Group N. There was 81% risk reduction of vasospasm in Group V than Group N, better survival with Group V with hazards ratio 5.89 times in Group N compared to Group V.

That can be might be due to the stimulation of AVPR1α overriding the potential beneficial effects of oxytocin receptor stimulation and increased NO release and thus, vasodilation could be a very useful tool for the prevention of severe cerebral vasospasm after SAH. Adding to this the effective vasoconstrictor augmenting effect on MAP which in turn increased the CPP and CBF.[11]

As regards results related to mortality, the cause was most probably from the vasospasm which leads to a decrease in vascular diameter hence an increase in cerebrovascular resistance. This is often followed by delayed cerebral ischemia leading to infarcts or even death. These discovered results were in agreement with Bele et al.[12] study on head trauma patients and they said that vasopressin possibly leads to vasodilation which helps in vasospasm prophylaxis after SAH.

As regards, GCS showed a significant decrease in Group N in comparison with Group V from 138 h to 168 h (due to occurrence of vasospasm). This can be explained by the effective action of vasopressin on MAP and CBF enriching the vasodilated cerebral arterial tree with effective CPP and CBF enough to maintain effective brain perfusion.

AVP safety obtained from our results according to organ functions, no significant changes between both Groups V and N. These results were in agreements with Albright et al.[13] and Farand et al.;[14] who stated that to obtain organ blood perfusion and maintained CPP, fluid resuscitation can be used, but vasopressors are usually added. Catecholamines are of choice, but side effects (e.g., tachycardia and myocardial O2 consumption increase) happens, especially with increasing dosage or prolonged duration, occur. The elevation of systemic vascular resistance can also compromise end-organ perfusion. In addition, refractoriness to catecholamines exists for those patients, AVP might be the drug of choice.[11]

One of the limitations of our study is being a single-center study. In addition, further studies are needed to compare the triple-H therapy with vasopressin infusion.

CONCLUSION

Vasopressin IVI improved MAP, CPP, and patient outcomes safely by reducing the incidence of cerebral vasospasm, and 28-day mortality after clipping or coiling of the cerebral aneurysm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.