Intravenous Fentanyl 4 μg per kg Administered before Scalp Pin Application is Inferior to Scalp Block in Preventing Hemodynamic Changes.

BACKGROUND: Application of scalp pins for craniotomy surgeries is a noxious stimulus, causing tachycardia and hypertension, resulting in increased cerebral blood flow and elevated intracranial pressure, hence measures to attenuate this will have beneficial role. AIMS: The aim is to compare the effectiveness of scalp block (SB) to 4 μg.kg-1 intravenous (i.v) fentanyl in attenuating hemodynamic response to scalp pin application in patients who underwent elective craniotomy under general anesthesia. SETTINGS AND
DESIGN: The study design involves prospective, randomized study conducted at Tertiary care center/hospital. SUBJECTS AND METHODS: Forty-four American Society of Anesthesiologists physical status Classes l and II patients were randomly allocated into the following groups: Group-SB (n = 22) received SB using 0.25% injection bupivacaine and Group-F (n = 22) received 1 μg.kg-1 i.v fentanyl. Patient's heart rate (HR) and mean arterial pressure (MAP) were recorded from the application of pins till 60 min and rescue analgesic/anesthetic agents and their dosage were noted. Statistical analysis was performed comparing HR and MAP changes to application of scalp pins. STATISTICAL ANALYSIS: Software developed by the Centre for Disease Control, Atlanta, namely Epidemiological Information Package 2010 was used to derive statistical variables.
RESULTS: Patients were comparable in age, gender, hypertension as comorbidity, baseline HR, and MAP. Significant rise in HR was noted in Group-F till 20th min compared to Group-SB. MAP was high from application of pins till 60th min in Group-F compared to Group-SB. Requirement of rescue analgesics/anesthetics was high in Group-F compared to Group-SB.
CONCLUSION: SB effectively attenuates hemodynamic response to application of scalp pins in patients undergoing elective craniotomy and reduces requirement of rescue analgesic and/or anesthetics. Copyright:

INTRODUCTION

Anesthetic management of patients undergoing craniotomy can often be challenging, because of underlying central nervous system pathology, complexity of surgery, and the need for meticulous postoperative management. The goals of neuroanesthesia in craniotomy patients are to ensure stable perioperative cerebral hemodynamics and to avoid sudden rise in intracranial pressure (ICP) to prevent acute brain swelling.

The application of skull pin holder and scalp incision during neurosurgical procedure produces a strong noxious stimulus and sympathetic activation, resulting in abrupt rise in heart rate (HR), blood pressure, and cerebral blood flow (CBF) under general anesthesia.[12] These cerebrovascular responses may result in elevated ICP and reduction in cerebral perfusion pressure, which can lead to cerebral ischemia, especially in patients with impaired autoregulation and compromised cerebral compliance.[3] Blocking sensory nerve supply of the scalp and periosteum would prevent the hemodynamic response to the application of skull pin.[4]

Various anesthetic and pharmacologic techniques, including local anesthetics, have been used to blunt this deleterious effect with variable success.[34567891011] Scalp block (SB) using local anesthetics is a popular, effective, and safe method in reducing the sympathetic response to the insertion of scalp pins. Multiple injections and increase in operating room time are the disadvantages of SB. Intravenous (i.v) fentanyl is commonly used in neurosurgical patients intended to attenuate the hemodynamic response to the insertion of pins.[5] This study was conducted to know the effectiveness of SB in comparison with i.v fentanyl in these patients.

Aim of the study

To compare the effectiveness of i.v fentanyl 4 μg.kg-1 bolus compared to SB using 0.25% injection bupivacaine, in attenuating the hemodynamic response to the placement of Sugita skull pin.

SUBJECTS AND METHODS

This was a prospective, randomized study undertaken over 2 years from October-2013 to September-2015 after obtaining prior approval from the Institutional Review Board (IRB) in a tertiary care center with approval number NH/IRB-CL-2013-121. Written and informed consent was obtained from all patients included in the study. Patients were sequentially and randomly assigned (by lottery pick method) to one of the two groups to receive either SB (Group-SB) or 1 μg.kg-1 i.v fentanyl bolus (Group-F). A total of 44 patients with the American Society of Anesthesiologists (ASA) physical status Classes I or II, aged between 18 and 60 years, with a Glasgow coma scale of more than 12/15, scheduled for elective craniotomies under general anesthesia where Sugita clamp would be used were included in the study.

Patients with the ASA physical Status III and above, emergency craniotomies, known or suspected allergy to local anesthetics or fentanyl, difficult airway, incision of craniotomy extending beyond the field of the SB, for example, craniofacial surgery, intracranial aneurysms and other neurovascular procedures, chronically treated with narcotic medications (more than 2 weeks) or surgeries where readjustment of pins may be necessary were excluded from the study. Patients with bleeding diathesis, coagulation abnormality, and known cardiac disease were also excluded from the study.

Patients in Group-F received 1 μg.kg-1 i.v fentanyl bolus 90s before clamp placement, while anesthesiologist blinded to the patients monitoring details administered SB in Group-SB using 0.25% bupivacaine, 5 min before clamp placement. Sample size was calculated using the following formula: (level of α)2× (standard deviation) 2/marginal error2. The minimum sample size required for the study was 44 using an α-level at 95% confidence level and power of 95% based on a previous study by Pinosky et al.[7]

Patients enrolled in this study underwent a preanesthetic evaluation and appropriate investigations were performed. Standard intra-operative monitoring included electrocardiograph, noninvasive blood pressure, arterial blood pressure (ABP), plethysmography, end-tidal CO2 (ETCO2), neuromuscular monitoring, and temperature monitoring. Baseline vital signs were recorded and a central venous catheter was placed under ultrasonographic guidance. After preoxygenation for 5 min, all patients were premedicated using injection fenatnyl 3 μg.kg-1. Anesthesia was induced using injection propofol 2 mg.kg-1, titrated to the response and neuromuscular blockade was achieved using injection vecuronium 0.1 mg.kg-1 after which laryngoscopy and endotracheal intubation was performed using reinforced endotracheal tube, fixed and firmly secured after confirming bilaterally equal air entry and sustained ETCO2 waveform. Radial artery was cannulated for ABP monitoring. Anesthesia was maintained using O2 and air, isoflurane (1%–1.5%), and injection vecuronium was supplemented as necessary.

Patients in Group-SB received SB by modified Pinosky et al. technique using 0.25% injection bupivacaine, 5 min before placing clamp.[7] Whereas those in Group-F received i.v injection fentanyl bolus (1 μg.kg-1) 90 s before clamp placement, i.e., a total of 4 μg.kg-1 of injection fentanyl intravenously in Group-F. HR, systolic blood pressure, diastolic blood pressure, and mean arterial pressure (MAP) were monitored continuously but were recorded at following intervals for the purpose of analysis of the study at baseline while preparing for the application of clamp, before clamp placement, before 1 μg.kg-1 injection fentanyl bolus (Group-F) and before SB (Group B), during clamp placement and at 30 s, 60 s, 5, 10, 20, 30, 45, and 60 min. The nerves blocked in Group-SB by modified Pinosky et al. technique of SB were bilateral supraorbital nerve, supratrochlear nerve, auriculotemporal nerve, zygomaticotemporal nerve, greater, lesser, and least occipital nerves.[7] Patients who had hemodynamic response to scalp pin application received additional dose of injection fentanyl and if necessary injection propofol in boluses of 10 mg titrated to the hemodynamic response. These additional doses received were also noted by the same anesthesiologist who recorded the parameters as mentioned above.

Statistical tools

Data collected were recorded in a master chart and analyzed using software developed by Centre for Disease Control, Atlanta, namely Epidemiological Information Package 2010. Range, frequency, percentage, mean, standard deviation, Chi-square, “t” value, and P values were calculated using this software. “t” test was used to test the significance of difference between quantitative variables and Yate's and Fisher's Chi-square tests for qualitative variables. A value of P < 0.05 was taken to denote significant relationship. Microsoft PowerPoint was used to prepare the graphs.

RESULTS

Analysis of the data showed that patients were comparable with respect to age (P = 0.4763, not significant [ns]) and gender (P = 0.1076, ns) and were statistically ns [Table 1]. Four patients in Group-SB and five patients in Group-F had preoperative hypertension as a comorbidity and were comparable (P = 0.512, ns). Baseline HR in Group-SB (85.8 ± 14.6) and Group-F (83.7 ± 10.4) (P = 0.5874, ns) and baseline MAP in Group-SB (91.6 ± 17.2) and Group-F (94.7 ± 10.4) (P = 0.4754, ns) [Tables 1 and 2] were comparable. Comparison of baseline hemodynamic variables between the two groups is displayed in Table 2. HR and mean arterial pressure (MAP) were comparable between the two groups after administration of fentanyl bolus or SB (P = 0.5251 for HR and P = 0.679 for MAP) [Table 3].

Table 1

Demographic data and baseline hemodynamic variables

Parameters	Group SB (n=22)	Group F (n=22)	P
Age (years)	20-55 (44.5±14.4)	25-58 (47.4±12.4)	0.4763 (NS)
Male:female	11:11	16:6	0.1076 (NS)
Preoperative hypertension (n), (present:absent)	4:18	5:17	0.512 (NS)

P<0.05 as significant. Group SB=Scalp block, Group F=Fentanyl group, n=Number of patients, NS=Not significant

Table 2

Basal hemodynamic values

Baseline values	Mean±SD		P
	Group SB	Group F
HR (rate/min)	85.8±14.6	83.7±10.4	0.5874 (NS)
SBP (mm of Hg)	127.6±26.2	128.7±13.3	0.8569 (NS)
DBP (mm of Hg)	74.8±14.2	78.3±9.8	0.3538 (NS)
MAP (mm of Hg)	91.6±17.2	94.7±10.4	0.4754 (NS)

P<0.05 as significant. SD=Standard deviation, NS=Not significant, HR=Heart rate, MAP=Mean arterial pressure, SBP=Systolic blood pressure, DBP=Diastolic blood pressure, Group SB=Scalp block, Group F=Fentanyl group

Table 3

Comparison of two groups with respect to heart rate and mean arterial pressure

Time	Mean±SD
	HR (bpm)			MAP
	Group SB	Group F	P	Group SB	Group F	P
After induction	85.8±14.6	83.7±10.4	0.5874 (NS)	91.6±17.2	94.7±10.4	0.4754 (NS)
After block/fentanyl	81.7±15.9	79.0±12.0	0.5251 (NS)	90.6±13.8	89.0±12.2	0.679 (NS)
At pin insertion	82.0±16.2	95.7±11.9	<0.001 (S)	91.2±15.1	104.8±11.8	0.0018 (S)
30 s	79.4±16.1	106.8±20.2	<0.001 (S)	89.8±15.2	115.1±13.8	<0.001 (S)
1 min	77.4±15.7	100.4±14.1	<0.001 (S)	87.7±14.2	110.3±13.4	<0.001 (S)
5 min	75.5±14.2	89.8±9.0	0.003 (S)	84.5±13.8	102.9±9.0	<0.001 (S)
10 min	74.2±12.9	84.8±8.0	0.0021 (S)	81.9±13.3	95.3±8.2	0.002 (S)
20 min	73.6±12.7	80.9±6.9	0.0222 (S)	79.6±13.7	92.6±8.7	0.005 (S)
30 min	76.0±11.6	79.9±5.9	0.176 (NS)	78.6±13.4	91.5±7.3	0.003 (S)
45 min	77.6±11.7	78.3±4.9	0.7885 (NS)	78.9±13.1	91.3±6.6	0.003 (S)
60 min	77.4±11.2	78.0±5.0	0.8097 (NS)	82.6±16.8	91.3±6.4	0.0294 (S)

P<0.05 as significant. S=Significant, NS=Not significant, Group SB=Scalp block, Group F=Fentanyl group, HR=Heart rate, MAP=Mean arterial pressure, SD=Standard deviation

However, after application of Sugita skull pins, statistically significant differences of HR and MAP were noted. Patients in Group-SB had favorable hemodynamic profile with respect to HR and blood pressure compared to Group-F [Table 3]. Patients in Group-F had statistically significant higher HR and blood pressure till 20th min, when compared to Group-SB [Table 3 and Figures 1, 2]. After 20th min, MAP continued to stay high in Group-F with statistically significant difference when compared to Group-SB [Table 3 and Figure 2].

Figure 1

Comparison of heart rate between the two groups. AI = After induction, AB = After block, AF = After fentanyl, Pin = Scalp pin application, Group-SB = Scalp block group, Group-F = Fentanyl group

Figure 2

Comparison of mean arterial blood pressure between the two groups. AI = After induction, AB = After block, AF = After fentanyl, Pin = Scalp pin application

DISCUSSION

Small incisions and narrow surgical window in craniotomy surgeries necessitate rigid head fixation and immobilization using scalp pins prior to neurosurgical intervention.[5] These pins pierce the layers of scalp and periosteum to the external lamina of the skull and presents as acute sympathetic activation with resultant rise in HR and blood pressure that can have deleterious effects in these patients. Abnormal autoregulation of CBF is often noted in these patients; hence, they are susceptible to small increase in ICP. Arterial hypertension can aggravate acute cerebral edema and resulting in herniation of brain.[1] This may also result in subarachnoid or intraparenchymal hemorrhage with intracranial vascular pathology. ICP rises very significantly in patients with preexisting intracranial hypertension at baseline and compensates poorly by volume compensation or intracranial compliance.[6] In susceptible patients, acute rise in blood pressure also leads to myocardial ischemia and pulmonary edema and hence, timely intervention to attenuate is necessary.[8]

In the present prospective, randomized study, hemodynamic changes associated with scalp pin application were least in patients who received SB (Group-SB) when compared to patients who received bolus 1 μg.kg-1 injection fentanyl. Both the groups did not differ with respect to age, gender, hypertension as comorbidity, baseline HR, and MAP [Tables 1 and 2]. Application of scalp pins resulted in significant changes in HR and blood pressure in Group-F when compared to Group-SB implying SB as an effective method in attenuating this response [Tables 3, 4 and Figures 1, 2]. Less requirement of rescue analgesic and/or anesthetic in GroupSB [Figure 3] implies the effectiveness of SB in attenuating hemodynamic response to scalp pin application. Patients in Group-F received injection fentanyl 1 μg.kg-1 in addition to 3 μg.kg-1 before induction of anesthesia. A total of 4 μg.kg-1 was the dose of i.v fentanyl used before scalp pin application in Group-F. Statistically significant hemodynamic changes were noted in these patients in spite of using this fentanyl dosage necessitating requirement of rescue injection fentanyl and/or injection propofol, whereas, 2 patients in Group-SB required rescue analgesia with i.v fentanyl. These observations imply that nociceptive stimulus of pin application is effectively blocked by this technique.

Table 4

Comparison of systolic and diastolic blood pressures between two groups

Time	Mean±SD
	SBP			DBP
	Group SB	Group F	P	Group SB	Group F	P
After induction	127.6±26.2	128.7±13.3	0.8569	74.8±14.2	78.3±9.8	0.3538
After block/fentanyl	121.5±19.7	121.0±15.5	0.9123	71.8±10.5	73.3±10.7	0.6421
At pin insertion	123.4±23.0	140.9±13.9	0.0039	72.3±11.3	87.4±10.3	<0.001
30 s	120.2±20.5	153.3±14.2	<0.001	71.4±12.0	97.3±14.3	<0.001
1 min	116.2±18.6	146.8±14.3	<0.001	69.8±11.9	93.3±14.0	<0.001
5 min	112.4±16.7	137.1±9.7	<0.001	68.6±12.4	85.8±9.6	<0.001
10 min	107.8±17.7	127.7±9.7	<0.001	66.4±12.5	79.5±8.2	0.002
20 min	106.6±20.6	125.5±9.0	0.003	63.8±11.5	76.9±8.7	<0.001
30 min	106.0±19.8	125.3±8.0	<0.001	63.5±10.1	75.4±7.1	<0.001
45 min	107.3±18.7	124.1±7.4	0.003	63.4±10.9	75.2±7.1	<0.001
60 min	112.2±20.4	123.8±7.3	0.006	68.0±11.0	75.3±7.5	0.0127

P<0.05 as significant. Group SB=Scalp block, Group F=Fentanyl group, SD=Standard deviation, SBP=Systolic blood pressure, DBP=Diastolic blood pressure

Figure 3

Comparison of rescue analgesic/anesthetic administered

α-agonists have been used to obtund the hemodynamic response in anesthesia and ICU settings.[9101112131415] They have also been used in craniotomy patients to achieve hemodynamic stability.[1617] Infiltration of local anesthetics for SB have been shown to be an effective method to abolish the hemodynamic response to skin incision or application of scalp pin.[18] Bupivacaine, lignocaine, ropivacaine, and mepivacaine have been safely used for SB.[3457181920]

A prospective, randomized control study was conducted on craniotomy patients with SB using 0.5% injection bupivacaine and concluded that, it is a very effective way to attenuate hemodynamic response to head pinning with reduced usage of supplemental anesthetics.[7] Statistically significant changes in HR and blood pressure were noted and isoflurane requirement was higher in control group when compared to patients who received SB.[7] The study correlates with this study in that the hemodynamic profile was better in patients who received SB when compared to patients who received fentanyl bolus [Tables 3 and 4]. Hemodynamic changes associated with pinning are undesirable and hence instead of having control group, we administered 1 μg.kg-1 injection fentanyl bolus for patients in the 2nd group. Requirement of supplemental analgesics and/or anesthetics was lower in patients receiving SB and results were comparable with the above study (P < 0.001) [Table 5].

Table 5

Rescue analgesic/anesthetic administered

Stat rescue medication administered	Group SB, n (%)	Group F, n (%)
Not required	19 (90.9)	-
Required	2 (9.1)	21 (100)
Fentanyl 50 μg	2 (9.1)	3 (13.6)
n Fentanyl 50 μg + Propofol 20 mg	-	4 (18.2)
Fentanyl 50 μg + propofol 30 mg	-	6 (27.3)
Fentanyl 50 μg + propofol 40 mg	-	4 (18.2)
Fentanyl 50 μg + propofol 50 mg	-	2 (9.1)
Fentanyl 50 μg + propofol 60 mg	-	3 (13.6)
P	<0.001 (significant)

P<0.05 as significant. Group SB=Scalp block, Group F=Fentanyl group

In our institute, SB for awake craniotomy is routinely administered by anesthesiologists, whereas it is practiced by neurosurgeon in patients who receive general anesthesia. In this study, SB was administered by anesthesiologist under general anesthesia after obtaining approval from the Intuitional Review Board so to compare its effectiveness when compared to 4 μg.kg-1 i.v fentanyl.

A study was conducted by infiltrating local anesthetics only at the site of pin insertion and hemodynamic parameters were noted while pinning. HR and blood pressure changes were least in these patients when compared to control group.[19] In our study, we opted for SB as this would also benefit these patients during craniotomy incision and during reapplication of scalp pins if necessitated. Using 0.25% injection bupivacaine for SB, a randomized, double-blind study was conducted and noted to have lesser changes in HR and blood pressure during the early stages of a frontotemporal craniotomy.[20] Similar to this study, we used 0.25% injection bupivacaine for SB in our study, but it was for all elective craniotomy patients and not limited to the frontotemporal region.

Reapplication of pins is likely in these patients resulting in sustained and exaggerated hemodynamic changes. SB as a technique, will have a sustained effect even during reapplication of scalp pins and hence advantageous when compared to i.v fentanyl bolus.[6] Although our study restricted to comparing hemodynamic attenuation during pin insertion, it was also observed that SB attenuated the hemodynamic response to skin incision, craniotomy, and dural opening which are also considered to be noxious stimulus. It was also observed that smooth extubation with better postoperative pain scores were achieved in patients who received SB.

The main limitation of this study was that we included patients with G.C.S of 12 and above and this could have an impact on the results obtained when compared to patients with G.C.S of 15. Advanced monitoring to assess intraoperative pain and to measure ICP was not used in our study. The other drawback of the study is multiple injections, sparing of nerves as seen with any regional technique, resulting in ineffective blockade. Future research with the inclusion of advanced monitoring methods to measure ICP and assess intraoperative pain and to correlate with hemodynamic changes would be encouraging. Studies using multimodal therapy of pain management with SB/fentanyl and nonsteroidal anti-inflammatory drugs would also be encouraging.

CONCLUSION

SB using 0.25% injection bupivacaine results in the sensory blockade, and is a very effective method compared to 4 μg.kg-1 i.v fentanyl to attenuate hemodynamic response to scalp pin application. It decreases the requirement of rescue analgesic/anesthetic agents following scalp pin application.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.