Comparison of Various Methods for Blunting the Hemodynamic Response to Skull Pin Insertion in Neurosurgical Patients: A Systematic Review

Abstract

Introduction

The application of skull pins can induce tachycardia and hypertension, potentially leading to intracerebral hemorrhage or elevated intracranial pressure. Both pharmacologic and non-pharmacologic modalities have been employed to mitigate these deleterious effects, with varying degrees of success.

Objective

We aimed to conduct a systematic review to assess and compare various strategies for preventing the hemodynamic response to skull pin insertion in neurosurgery.

Materials and Methods

We searched the PubMed, Google Scholar, and Cochrane Library databases, along with forward and backward citations, up to May 2024. Randomized controlled trials investigating methods used to blunt the hemodynamic response to skull pin application in neurosurgical patients were included. A qualitative review was performed on the effects of local anesthesia (LA), comparisons between local and intravenous agents, as well as the use of α-agonists and opioids. The quality of evidence was assessed using the Risk of Bias-2 tool. This study is registered on PROSPERO (CRD42024485232).

Results

Of the 10,812 records identified, 54 studies were included, the majority of which had either low or some concerns regarding the risk of bias. In 45% of the studies, local infiltration alone was effective in preventing the hemodynamic response. Similarly, scalp block alone was effective in 92.3% of trials. Both clonidine and dexmedetomidine were found to be effective in most studies, whereas opioids were ineffective in 50% of the trials. When comparing LA with IV agents, 62.5% of studies reported that both methods were equally effective.

Conclusion

Among methods evaluated, scalp block and dexmedetomidine (particularly at 1 µg/kg IV) consistently demonstrated high efficacy in blunting the hemodynamic response to skull pin insertion. Clonidine also showed robust effectiveness across studies. Local infiltration was beneficial in most, but not all cases, while opioids and β-blockers showed variable or limited efficacy.

 

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Keywords

neurosurgery - hemodynamics - hypertension - tachycardia - skull pin

Background

Head holders or skull pins are routinely used in neurosurgery to stabilize the head during both cranial and cervical spine surgeries. They are also useful for intraoperative neuronavigation. The most commonly used types are the Mayfield and Sugita head holders. Skull pins penetrate the scalp and periosteum before embedding into the outer layer of the skull. The application process is known to be painful and elicits a hemodynamic response, including tachycardia and hypertension. This can further lead to complications such as intracerebral hemorrhage or aneurysmal and tumor-related bleeding.[1] Various pharmacologic and non-pharmacologic modalities have been proposed to mitigate these effects, including regional anesthesia, opioids, β-blockers, and α-agonists, with varying degrees of success. Numerous trials have been conducted to determine the superiority of one method over another.

However, this topic has not been systematically reviewed in the literature. Hence, this review was conducted to assess and compare various modalities used to prevent the hemodynamic response to skull pin insertion in the neurosurgical patient population.

 

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Methods

The methodology adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was prospectively registered in the international systematic review registry (PROSPERO)—CRD42024485232.

Search Strategy

The databases PubMed, Google Scholar, and the Cochrane Library (from inception to May 2024) were searched by two authors (C.K. and U.B.), and the procedure was reviewed by two authors (P.L. and P.P.). The following keywords were used in the search: hemodynamics or “blood pressure” or “heart rate” or hypertension or tachycardia or “pulse rate” or hemodynamic and “skull pin” or Mayfield or Sugita or “head fixation device” or “head holder” or “skull clamp” and neurosurgery or craniotomy or “neurological procedures.” A manual search of the reference lists from the selected articles was conducted to identify additional trials. The search was restricted to English-language and human studies. The last search was conducted on May 9, 2024.

 

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Selection Criteria

Two independent reviewers (C.K. and N.G.) evaluated the search results, and eligible studies were identified for possible inclusion using predefined selection criteria.

Inclusion criteria: Randomized controlled trials (RCTs) investigating methods used to blunt the hemodynamic response to skull pin or head holder application under general anesthesia.

Exclusion criteria: Studies published in languages other than English, unavailability of full-text articles, review articles, letters to the editor, conference reports, and retrospective or prospective cohort studies.

Any disagreements between the authors were resolved through discussion or consulting the primary author (C.K.).

 

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Methodological Quality Assessment

The methodological quality assessment of each trial was independently performed by two authors (A.K.B.C. and N.G.) using the Risk of Bias-2 tool.[2]

 

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Data Extraction and Synthesis

An independently created template was used to extract and compare data. The primary outcome was to evaluate whether the method or intervention effectively blunted the hemodynamic response—that is, whether there was no statistically significant rise in heart rate (HR) and blood pressure (BP) after skull pin insertion. Secondary outcomes included identifying the types of agents used and assessing the occurrence of any adverse events. Extracted data included study design, characteristics of the study population, type of skull pin used, interventions, and outcomes related to the prevention of HR and BP responses to skull pin insertion (i.e., whether the method prevented a significant rise in HR and BP after skull pin insertion), as well as any reported adverse events.

The included studies exhibited significant variations in study design and methodology. These variations were observed in the study population, type, and the modalities used to blunt the hemodynamic response. Therefore, only a qualitative analysis of the data was conducted.

 

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Results

Characteristics of Included Trials

The search strategy initially yielded 10,812 citations: 9,920 from Google Scholar, 796 from PubMed, and 96 from the Cochrane Library ([Fig. 1]). After screening titles and abstracts and removing duplicate records, review articles, letters to the editor, non-English-language articles, and animal studies, 51 articles were selected. After screening the references of these 51 articles, an additional 3 articles were included.

Fig. 1 PRISMA flow diagram illustrating the study selection process. A total of 10,812 records were initially identified through database searches. After screening and applying inclusion criteria, 51 full-text articles were assessed for eligibility. An additional three relevant studies were identified from references, resulting in a total of 54 studies included in the final analysis.

Ultimately, 54 studies (total study subjects = 3,104) were included in the analysis. The PICO (population, intervention, comparator, outcome) characteristics of the studies are summarized in [Table 1]. The sample size of study subjects ranged from 12 to 120.

Table 1 Characteristics of the included studies

Author	Type	Population	Intervention and comparison	Outcome (with respect to prevention of HR and BP response to skull pin insertion and adverse events)
Akcil et al[18]	RCT	ASA class I–III patients aged between 18 and 70 y scheduled for elective infratentorial craniotomy (n = 45)	SB with 0.5% bupivacaine vs. infiltration with bupivacaine 0.5% vs. IV remifentanil 50 µg bolus	SB was better. Local infiltration only blunted the HR response Adverse events—not assessed
Akshaya et al[23]	RCT	Sixty patients of aged 15–75 y of both sexes posted for elective neurosurgery with ASA grading I, II, and III with GCS of ≥ 8 (n = 60)	SB with 0.5% bupivacaine vs. dexmedetomidine 0.5 µg/kg IV loading followed by 0.25 g/kg/h	Both SB with bupivacaine and dexmedetomidine IV were equally effective. Adverse events—not assessed
Altaf et al[24]	RCT	ASA I and II, either sex, aged between 18 and 65 y, undergoing elective craniotomy for newly diagnosed supratentorial brain lesions (n = 100)	2 µg/kg fentanyl IV bolus vs. SB with 0.5% levobupivacaine	Both methods had an increase in HR and BP, but more with fentanyl Adverse events—none
Arunashree et al[25]	RCT	ASA I or II, between 18 and 60 y, with a GCS of more than 12/15, for elective craniotomies (n = 44)	SB using 0.25% bupivacaine Vs. 1 μg/kg IV fentanyl	SB was effective Adverse events—not assessed
Bala et al[26]	RCT	Patients aged 18–65 y, ASA I to II, elective craniotomy (n = 88)	0.75 µg/kg dexmedetomidine IV vs. 0.5% ropivacaine infiltration	Both dexmedetomidine IV and ropivacaine infiltration were effective. Hypotensive events were more with IV dexmedetomidine than with pin site infiltration of ropivacaine
Bharne et al[3]	RCT	18–60 y ASA physical status I and II, elective neurosurgical procedure (n = 66)	IV labetalol 0.25 mg/kg vs. SB with 0.25% bupivacaine	SB was more effective Adverse events—none
Bithal et al[19]	RCT	30 children (ASA I/II), age below 12 y, elective suboccipital craniectomy (n = 30)	Pin site 1% lignocaine infiltration vs. control	Infiltration with 0.5% lignocaine plain failed to prevent the hemodynamic changes up to 1 min after the pin's placement. However, the technique successfully blocked these changes beyond 1 min post skull pins fixation. Adverse events—not assessed
Bloomfield et al[4]	RCT	ASA II or III, age 18–68 y undergoing elective craniotomy for resection of a supratentorial tumor, clipping of an unruptured cerebral aneurysm, or removal of an epileptic focus (n = 36)	Infiltration with bupivacaine (0.25%) and epinephrine (1:200,000) vs. infiltration with saline/epinephrine (1:200,000)	Infiltration with bupivacaine and epinephrine was effective Adverse events—not assessed
Can et al[27]	RCT	ASA I or II; age 18–85 y (n = 90)	SB with 0.5% bupivacaine vs. 0.5% levobupivacaine vs. saline as a placebo	SB with both bupivacaine and levobupivacaine was equally effective Adverse events—none
Carella et al[28]	RCT	ASA I, II, and III patients, elective supratentorial intracranial surgery (n = 60)	SB with 0.33% levobupivacaine vs. saline block	SB was better Adverse events—not assessed
Chadha et al[45]	RCT	Normotensive patients, ASA I and II, scheduled for supratentorial surgery (n = 58)	Oral clonidine 3.6 µg/kg vs. oral diazepam 2 mg/kg	Oral clonidine was effective Adverse events—none
Colley et al[5]	RCT	n = 12	0.5%lignocaine infiltration vs. placebo	Lignocaine infiltration was effective Adverse events—not assessed
Costello et al[46]	RCT	Elective craniotomy, aged 18–70 y, weighing 45–108 kg (n = 50)	Oral clonidine 3 µg/kg vs. oral temazepam 10–20 mg	Oral clonidine was effective Adverse events—not assessed
Dash et al[29]	RCT	Supratentorial craniotomies (n = 60)	SB with bupivacaine 0.25% vs. SB with bupivacaine 0.25% and clonidine 2 μg/kg (adjuvant) vs. SB with bupivacaine 0.25% plus clonidine 2 μg/kg IV	Both SB with clonidine as an adjuvant and SB with IV clonidine were equally effective Adverse events—not assessed
Dawlatly et al[12]	RCT	ASA I and II, elective craniotomy, 16–60 y (n = 28)	Dexmedetomidine 0.25 µg/kg IV vs. lidocaine 1% infiltration vs. dexmedetomidine plus lidocaine combined vs. placebo	Dexmedetomidine alone or in combination with lidocaine infiltration was both effective Adverse events—not assessed
Deshmukh et al[30]	RCT	ASA I and II undergoing elective supratentorial craniotomy (n = 60)	SB with 0.5% levobupivacaine vs. 0.5% ropivacaine	Both methods were effective HR was lower with levobupivacaine SB Adverse events—not documented
Dhanasekaran et al[13]	RCT	ASA I and II patients of age 16–40 y, scheduled for elective craniotomy for intracranial tumor resection (n = 40)	Placebo tablet with 2% lignocaine infiltration vs. 900 mg of gabapentin along with 2% lignocaine scalp infiltration	Gabapentin with lignocaine infiltration was more effective Adverse events—not documented
Doblar et al[6]	RCT	Adult patients undergoing intracranial or spinal surgery requiring the use of headrest skull pins (n = 40)	Alfentanil 10 µg/kg IV vs. esmolol 1 mg/kg vs. thiopental 1.5 mg/kg vs. infiltration with 0.5% xylocaine	IV alfentanil and local infiltration with xylocaine both were effective Adverse events—not documented
Elkafrawy et al[62]	RCT	18–60 y of both genders, ASA I and II (n = 60)	50 mg/kg magnesium sulfate (MgSO4) IV in 100 mL 0.9 sodium chloride vs. 100 mL 0.9% sodium chloride	MgSO4 IV was effective Adverse events—none
Ganeriwal et al[31]	RCT	ASA I or II between age 18 and 60 y of either sex who underwent elective supratentorial craniotomy (n = 60)	SB with 0.25% bupivacaine vs. SB with 0.25% levobupivacaine	Both bupivacaine and levobupivacaine were equally effective Adverse events—none
Gazoni et al[41]	RCT	Age >18 y (n = 30)	SB with 0.5% ropivacaine vs. no block	SB was ineffective Adverse events—not documented
Geze et al[20]	RCT	ASA I or II patients of either sex aged between 18 and 60 y (n = 45)	0.5% bupivacaine infiltration vs. SB with 0.5% bupivacaine vs. neither SB nor infiltration	SB only was effective Adverse events—not documented
Hussien et al[32]	RCT	Patients aged 21–60 y of both genders and ASA grade I–II to undergo craniotomy for supratentorial tumors, body mass index <35 kg/m2 (n = 30)	SB with bupivacaine 0.5%/lidocaine 2% mixture with epinephrine 1:200,000 vs. no block	SB was effective Adverse events—not documented
Jellish et al[7]	RCT	ASA I–III, age range 18–65 y (n = 34)	Clonidine 5 µg/kg per oral plus 1% lignocaine pin site infiltration vs. clonidine with saline infiltration vs. placebo with lignocaine infiltration vs. placebo with saline infiltration	Oral clonidine plus lignocaine infiltration and lignocaine infiltration alone both were effective Adverse events—not documented
Kondavagilu et al[49]	RCT	18–60 y, ASA I–III, undergoing elective neurosurgical procedure (n = 90)	1 μg/kg of IV dexmedetomidine vs. 0.5 μg/kg of IV dexmedetomidine vs. normal saline	Both methods were effective Adverse events—none
Konwar et al[33]	RCT	ASA class I and II, age 18–65 y, elective surgery, preoperative GCS 15 (n = 79)	SB with 0.5% levobupivacaine vs. dexmedetomidine infusion 1 µg/kg over 10 min before induction of anesthesia, followed by a maintenance of 1 µg/kg/h from the time of intubation till 30 min after skull pin application	Both methods were effective Adverse events—none
Kundra et al[14]	RCT	ASA I and II of either sex between 18 and 60 y, undergoing elective craniotomy for intracranial tumor surgery in the supine position (n = 60)	Oral gabapentin 900 mg plus 2% lignocaine infiltration vs. placebo plus 2% lignocaine infiltration	Gabapentin plus lignocaine infiltration was better Adverse events—negligible
Levin et al[8]	RCT	Adult patients for elective craniotomy (n = 20)	Infiltration of 0.5% mepivacaine with epinephrine 5 µg/mL vs. placebo	Mepivacaine with adrenaline infiltration was effective Adverse events—not documented
Makwama et al[47]	RCT	18–70 y, 40–108 kg and ASA grade I and II (n = 50)	IV clonidine 2 µg/kg vs. saline	IV clonidine was effective Adverse events—only 2 patients in the clonidine group developed bradycardia, the maximum decrease in HR was up to 55 bpm and treated with glycopyrrolate
Misra et al[15]	RCT	ASA class I and II patients of either sex aged between 18 and 60 y, undergoing planned elective craniotomy for intracranial tumor in supine position (n = 47)	Oral placebo plus 2% lidocaine infiltration at pin sites vs. oral gabapentin 900 mg plus normal saline infiltration vs. oral gabapentin 900 mg plus 2% lidocaine infiltration	Oral gabapentin, along with lidocaine scalp infiltration, was effective. Oral gabapentin alone significantly attenuated the BP; however, HR responses were more variable. Adverse events—not documented
Morina et al[16]	RCT	ASA I–II, aged 30–62 y, of both sexes (n = 108)	2 µg/kg fentanyl IV vs. infiltration with 0.5% bupivacaine vs. both methods together	Fentanyl IV combined with bupivacaine infiltration was effective Adverse events—not documented
Mushtaq et al[50]	RCT	ASA class I or II and aged between 18 and 70 y (n = 60)	Single bolus dose of dexmedetomidine (1 µg/kg) IV over 10 min vs. placebo	IV dexmedetomidine was effective Adverse events—not documented
Nagappa et al[42]	RCT	Patients undergoing elective craniotomy (n = 64)	SB with ropivacaine 0.25% vs. 2 µg/kg IV clonidine	IV clonidine was better Adverse events—none
Nanjundaswamy et al[48]	RCT	Elective craniotomies, ASA I and II, age group of 18–70 y without any history of allergy to study drugs (n = 60)	Clonidine 2 µg/kg IV vs. lignocaine 1.5 mg/kg IV	Both methods were effective. IV clonidine was better than lignocaine. Adverse events—not documented
Özköse et al[17]	RCT	ASA I–II, elective craniotomies for intracranial tumor or aneurysm (n = 45)	2 µg/kg fentanyl IV vs. 1% plain lidocaine infiltration vs. both methods applied together	Combination of IV fentanyl and lidocaine infiltration was effective. Adverse events—not documented
Patel et al[55]	RCT	Patients aged between 18 and 65 y, weighing 40–70 kg, belonging to ASA grade I or II, undergoing elective neurosurgery (n = 50)	IV labetalol 0.25 mg/kg and IV fentanyl 2 µg/kg vs. IV fentanyl 2 µg/kg only	Combination of labetalol and fentanyl was effective. Adverse events—none
Paul et al[9]	RCT	Patients aged between 18 and 70 y, belonging to ASA 1 or 2, scheduled for elective craniotomy in supine or lateral position (n = 52)	1 μg/kg dexmedetomidine IV over 10 min vs. 2% lignocaine infiltration at pin application sites	Both methods were comparable Adverse event—incidence of hypotension and/or bradycardia was significantly greater in the dexmedetomidine group
Pinosky et al[34]	RCT	Patients between the ages of 18 and 85 y; ASA I, II, or III, undergoing elective craniotomy for tumors (n = 21)	Placebo vs. SB with 0.5% bupivacaine	SB was effective Adverse events—none
Praveena et al[44]	RCT	ASA I–II, between 18 and 60 y, elective supratentorial craniotomy for space-occupying lesion (n = 80)	Fentanyl 1 µg/kg as adjuvant to 20 mL of 0.25% bupivacaine in SB vs. dexmedetomidine 1 µg/kg as adjuvant to 20 mL 0.25% bupivacaine in SB	Dexmedetomidine with bupivacaine in SB was more effective Adverse events—not documented
Ramesh et al[35]	RCT	ASA I and II, either sex, aged between 18 and 65 y, undergoing elective craniotomy (n = 60)	SB with 0.5% bupivacaine vs. SB with 0.5% levobupivacaine	Both methods are equally effective. Adverse events—none
Renganathan et al[51]	RCT	Patients posted for elective craniotomy in the age group of 18 to 60 y of both sexes (n = 40)	Dexmedetomidine 1 µg/kg over 10 min vs. normal saline	Dexmedetomidine bolus was effective. Adverse events—not documented
Sahana et al[43]	RCT	18–65 y, ASA I and II for elective craniotomies (n = 60)	SB with 0.5% ropivacaine added with either normal saline vs. dexmedetomidine (1 µg/kg) as an additive	Both were ineffective. Adverse events—not documented
Saringcarinkul et al[52]	RCT	ASA I to III, scheduled for elective supratentorial craniotomy (n = 30)	Dexmedetomidine IV 1 μg/kg over 10 min followed by 0.6 μg/kg/h vs. fentanyl 2 μg/kg IV	Both methods were comparable Adverse events- not documented
Sekhar et al[21]	RCT	ASA class I and II aged between 18 and 65 y undergoing elective supratentorial craniotomies (n = 60)	SB with 0.5% bupivacaine vs. local infiltration at pin-insertion site with 0.5% bupivacaine	SB was effective Adverse events—not documented
Shah et al[10]	RCT	ASA 1 and 2, aged 20–70 y undergoing elective craniotomy surgery, having preoperative GCS 15 (n = 60)	Local infiltration with 0.5% ropivacaine vs. infiltration with 1% lignocaine with adrenaline	Infiltration with ropivacaine was effective. Adverse events—none
Shekhar et al[53]	RCT	ASA I–II, aged 18–60 y, having GCS score 13–15, scheduled for elective craniotomy for intracranial tumor excision (n = 105)	Bolus IV infusion of dexmedetomidine 1 µg/kg over 15 min followed by 0.5 µg/kg/h vs. bolus IV infusion of lignocaine 2 mg/kg over 15 min followed by 1.5 mg/kg/h vs. normal saline	Dexmedetomidine infusion was better Adverse events—not documented
Singh D et al[36]	RCT	18–60 y, ASA class I and II, who underwent elective craniotomy (n = 90)	SB with bupivacaine 0.5% vs. SB with ropivacaine 0.5%	Both methods were equally effective Adverse events— none
Singh G et al[37]	RCT	ASA I and II patients aged between 18 and 65 y with a preoperative GCS score of 15 undergoing elective craniotomy (n = 65)	1 µg/kg of dexmedetomidine IV bolus followed by an infusion of 1 µg/kg/h vs. SB with 0.5% ropivacaine	Only SB with ropivacaine was effective Adverse events— none
Smith et al[38]	RCT	ASA I or II patients with a GCS count of more than 12/15, scheduled for any procedure with the Mayfield clamp (n = 22)	Alfentanil 10 µg/kg vs. SB with lignocaine1%	SB was more effective Adverse events—not documented
Theerth et al[22]	RCT	Adult patients (18–65 y) (n = 60)	SB with a mixture of 10 mL of lignocaine 2% with adrenaline 1:200,000 concentration and 10 mL of bupivacaine 0.5% vs. infiltration pin site with the same above mixture	Significant rise of HR and BP after pin insertion in both groups. But the increase was more in the infiltration group. Adverse events—not documented
Thongrong et al[54]	RCT	18 and 64 y, belonging to the ASA I and II (n = 60)	Dexmedetomidine 1 µg/kg IV vs. fentanyl 1 µg/kg IV	Dexmedetomidine was better. Adverse events—hypotension events have a higher incidence in the dexmedetomidine group
Tuchinda et al[39]	RCT	ASA I and II patients aged 16–65 y, undergoing elective supratentorial craniotomy (n = 60)	SB with 0.5% bupivacaine and 1:200,000 adrenaline vs. SB with 0.25% bupivacaine and 1:200,000 adrenaline vs. SB using normal saline with 1:200,000 adrenaline	Both concentrations of bupivacaine (0.25 and 0.5%), with 1:200,000 adrenaline for SB blunted BP but not the HR response. Adverse events—not documented
Wajekar et al[40]	RCT	ASA grades I and II, aged 18–65 y, GCS 15/15, scheduled for supratentorial craniotomies, with duration lasting 60–360 min (n = 60)	SB with clonidine 2 μg/kg with 0.25% bupivacaine vs. SB with plain 0.25% bupivacaine	SB with clonidine as an adjuvant was more effective. Adverse events—not documented
Yildiz et al[11]	RCT	ASA I–II patients scheduled for elective craniotomy (n = 120)	Fentanyl 2 µg/kg IV vs. infiltration with 0.25% bupivacaine plus 2 µg/kg fentanyl IV	Both methods were equally effective. Adverse events—none

Abbreviations: ASA, American Society of Anesthesiologists; IV, intravenous; RCT, randomized controlled trial; SB, scalp block.

A total of 54 RCTs were included. The different methods investigated are summarized in [Fig. 2].

Fig. 2 Distribution of different agents and techniques used for analgesia during head fixation in the included studies. Scalp block was the most commonly employed method (n = 26), followed by local infiltration (n = 21), dexmedetomidine (n = 14), opioids (n = 13), miscellaneous agents (n = 10), and clonidine (n = 8).

The Mayfield head holder was used in 24 studies, while the Sugita head holder was used in 3 studies. The type of head holder used in the remaining 27 studies was not specified.

 

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Methodological Quality Assessment

The risk of bias was low in 11 studies, had some concerns in 41 studies, and was high in 2 studies ([Fig. 3]).

Fig. 3 Summary plot showing the risk of bias assessment for RCTs.

 

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Effect of Local Infiltration

Infiltration of local anesthesia (LA) was performed in 20 out of 56 studies ([Table 1]). Among these, nine studies (45%) found that local infiltration alone was effective,[3] [4] [5] [6] [7] [8] [9] [10] [11] while seven studies (35%) reported that local infiltration combined with an intravenous (IV) or oral method was effective.[7] [12] [13] [14] [15] [16] [17] Thus, a total of 15 studies (75%) demonstrated the effectiveness of local infiltration. However, five studies (25%) found local infiltration to be ineffective in preventing the hemodynamic response.[18] [19] [20] [21] [22]

Regarding the agents used for infiltration, the most commonly used were 2% plain lignocaine[9] [13] [14] [15] and 0.5% bupivacaine.[16] [18] [20] [21] Three studies used 1% lignocaine[7] [12] [17] and 0.5% lignocaine.[5] [6] [19] Additionally, one study used lignocaine with adrenaline,[10] two studies used 0.5% ropivacaine,[3] [10] one study used 0.25% bupivacaine with adrenaline,[4] one study used 0.5% mepivacaine with adrenaline,[8] one study used 0.25% bupivacaine,[11] and one study used a mixture of 1% lignocaine with adrenaline and 0.25% bupivacaine.[22]

 

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Effect of Scalp Block

Scalp block (SB) was investigated in 26 of the 54 included studies ([Table 1]). Of these, 24 studies (92.3%) reported that SB alone was effective in blunting the hemodynamic response.[18] [20] [21] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] However, SB was found to be ineffective in three studies (11.5%).[41] [42] [43] One study found that SB with clonidine as an adjuvant and SB with IV clonidine were equally effective.[29] Another study reported that dexmedetomidine as an adjunct to bupivacaine in SB was more effective than fentanyl as an adjunct.[44]

Bupivacaine was the most frequently utilized local anesthetic for SB, employed in 15 studies.[18] [20] [21] [23] [25] [26] [27] [29] [31] [34] [35] [36] [39] [40] [44] Levobupivacaine was used in seven studies,[24] [27] [28] [30] [31] [33] [35] while ropivacaine was reported in five studies.[30] [36] [41] [42] [43] Lignocaine was evaluated in a single study.[38] A few studies utilized a combination of bupivacaine and lignocaine.[22] [32] Concerning adjuvants, clonidine was incorporated in two studies,[29] [40] dexmedetomidine in two studies,[43] [44] and fentanyl in one study.[44]

 

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Effect of Clonidine

Clonidine was investigated in 8 out of 54 studies ([Table 1]). Six studies showed that clonidine alone was effective,[29] [42] [45] [46] [47] [48] while two studies found that clonidine, when combined with other methods or given as an adjuvant to LA, was effective.[7] [40] Thus, all eight studies demonstrated a positive result regarding the blunting of the hemodynamic response through prior clonidine administration, either alone or in combination with another agent, without any side effects.

IV clonidine was used in four studies,[29] [42] [47] [48] oral clonidine in three studies,[7] [45] [46] and as an adjuvant to LA in two studies[29] [40] ([Table 1]). In all studies involving IV clonidine, it was administered at a dose of 2 μg/kg, while oral clonidine was given at doses of 3, 3.6, and 5 μg/kg.

 

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Effect of Dexmedetomidine

Fourteen out of 54 studies (25.9%) investigated the effect of dexmedetomidine on the hemodynamic response ([Table 1]). Twelve studies (85.7%) found that dexmedetomidine alone was effective.[3] [9] [12] [23] [33] [44] [49] [50] [51] [52] [53] [54] Only two studies (14.3%) found it ineffective.[37] [43]

In 10 of the 14 studies evaluating dexmedetomidine, it was administered as a bolus IV dose of 1 µg/kg before pin application.[9] [21] [33] [37] [43] [49] [50] [51] [52] [54] In three studies, it was given at a lower dose of 0.25, 0.5, or 0.75 µg/kg IV bolus.[3] [12] [23] In two studies, dexmedetomidine was used as an adjuvant to LA in SB at a dose of 1 µg/kg.[43] [44]

 

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Effect of Opioids

Twelve studies ([Table 1]) used opioids to prevent the response to pin insertion. Three studies (25%) found that opioid bolus alone was effective,[6] [11] [52] and three studies (25%) found that opioids combined with LA were effective.[16] [17] [55] Six studies (50%) found opioids to be ineffective.[18] [24] [25] [38] [44] [54]

Fentanyl was the most commonly used opioid, employed in nine studies.[11] [16] [17] [24] [25] [52] [54] [55] Alfentanil was used in two studies,[6] [38] and remifentanil was used in one study.[18]

 

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Comparison of Local Anesthesia with Intravenous Agents

Sixteen studies compared LA with IV drugs, as summarized in [Table 1]. Of these 16 studies, 5 (31.25%) demonstrated that LA was superior to IV agents, and only 1 study (6.25%) found that an IV agent was more effective than LA in blunting the hemodynamic response ([Fig. 2]).

SB was found to be superior in five out of the nine studies in which SB was given and compared with IV agents.[18] [25] [26] [37] [38] For SB, 0.25% bupivacaine was used by two authors,[25] [26] 0.5% bupivacaine was used by two authors,[18] [23] 0.5% levobupivacaine was used by two authors,[24] [33] 0.25% ropivacaine was used by one author,[42] 0.5% ropivacaine was used by one author,[37] and 1% lignocaine was used in one study.[38]

One study comparing 0.25% ropivacaine for SB with IV clonidine reported that the IV agent was more effective in attenuating the hemodynamic response to skull pinning.[42] This was the only study in which an IV agent alone demonstrated superior efficacy compared with a local anesthetic. Another study found that IV alfentanil and lignocaine infiltration effectively prevented the hemodynamic response, whereas thiopental and esmolol were not.[6] Altaf et al compared SB with 0.5% levobupivacaine to IV fentanyl bolus and noted that neither method prevented the hemodynamic response to skull pinning.[24]

Five studies found both LA and IV agents to be effective.[3] [6] [9] [11] [33] A couple of studies showed that a combination of LA and IV agents was superior to either method alone.[16] [17] El-Dawlatly et al observed that IV dexmedetomidine, alone or in combination with LA infiltration, effectively prevented rises in HR and BP, whereas LA infiltration alone was ineffective.[12]

 

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Miscellaneous Agents

Three authors studied β-blockers. Two studies found them to be ineffective.[6] [26] Patel et al found that a combination of IV labetalol and fentanyl was effective.[55] Oral premedication with benzodiazepines was studied in two trials, with none showing positive results. Three authors studied a combination of oral gabapentin and local infiltration, and all the studies showed prevention of the hemodynamic surge. Doblar et al investigated the effect of an IV thiopental bolus and found it ineffective.[6] A single study showed that an IV bolus of magnesium sulfate successfully prevented the hemodynamic response.

 

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Adverse Events

Incidents of hypotensive episodes were associated with IV dexmedetomidine in three studies.[3] [9] [54] Instances of bradycardia were found with IV clonidine and dexmedetomidine.[9] [47]

 

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Discussion

This review highlights various pharmacological and regional techniques investigated for attenuating the hemodynamic response associated with skull pin insertion in neurosurgical procedures. The interventions analyzed include LA infiltration, SB, α-2 adrenergic agonists (clonidine and dexmedetomidine), opioid administration, and miscellaneous agents such as β-blockers, IV lignocaine, oral gabapentin, benzodiazepines, thiopentone, and magnesium ([Fig. 4]). Among these, local infiltration and SB—alone or in combination with systemic agents—were consistently reported to be effective in blunting the sympathetic response.

Fig. 4 Schematic representation of pharmacological strategies used to prevent hemodynamic responses to skull pin application during neurosurgical procedures. The central goal is attenuation of nociceptive stimulus, achieved through local infiltration, scalp block, opioids, α-2 agonists (e.g., clonidine, dexmedetomidine), and miscellaneous agents including β-blockers, magnesium, and gabapentin.

Skull pin application, essential for head fixation during cranial and spinal surgeries, induces a potent nociceptive stimulus. This can result in a marked increase in sympathetic tone, manifesting as abrupt hypertension and tachycardia, which may escalate intracranial pressure (ICP), cerebral blood flow (CBF), or contribute to cerebral edema. Such responses pose significant risks, particularly in patients with impaired intracranial compliance or autoregulatory dysfunction. Therefore, preventing these transient yet potentially hazardous hemodynamic perturbations is critical to patient safety.

Regional Anesthetic Techniques: Local Infiltration versus Scalp Block

Regional anesthesia techniques, notably LA pin-site infiltration and SB, have been widely employed due to their direct mechanism of action and favorable safety profile. Pin-site infiltration is a technically simple, time-efficient, and resource-light intervention. It offers targeted anesthesia and is often sufficient when administered accurately before skull pin insertion. However, its efficacy is limited to the specific injection site and may necessitate re-administration if pin repositioning occurs.

SB, on the other hand, provides more extensive coverage by anesthetizing the sensory nerves supplying the scalp, including the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, and occipital nerves. This technique offers a longer duration of analgesia, benefiting not only during pin insertion but also for subsequent surgical steps such as incision, craniotomy, and dural opening. Furthermore, SB facilitates flexibility in pin placement across the scalp. Despite these advantages, SB requires greater expertise, longer preparation time, and larger volumes of local anesthetic. Both regional techniques carry procedural risks such as inadvertent intravascular injection and needlestick injury.

 

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Duration of Efficacy of Drugs/Modalities

The duration of efficacy of various drugs and techniques used to attenuate the noxious stimuli during pinning is influenced by the pharmacological characteristics of the agents and the timing and route of administration. A meta-analysis of studies assessing the timing of SB revealed that the duration of postoperative analgesia varied depending on whether the block was administered pre-incision or at wound closure.[56] Data showed that preoperative SB significantly reduced postoperative pain scores for up to 4 hours. SB using long-acting local anesthetics like bupivacaine or ropivacaine generally provides reliable, extended analgesia that spans both intraoperative and early postoperative periods. The duration may be further enhanced by the addition of vasoconstrictors such as epinephrine or adjuvants such as dexmedetomidine, clonidine, fentanyl, or dexamethasone, which prolong the anesthetic effect through various mechanisms, including vasoconstriction and synergistic central action.[40] [44] Systemic agents vary in duration; dexmedetomidine has a rapid onset and moderate duration but may require a continuous infusion for sustained efficacy, while clonidine, due to its longer half-life, offers more prolonged effects. Local infiltration with short-acting agents like lignocaine provides a limited duration unless supplemented with adjuvants or longer-acting drugs. Opioids and β-blockers, although commonly used, typically provide only short-term attenuation and often necessitate repeated dosing or infusion for sustained control. Therefore, the optimal choice of modality should be tailored to the expected intensity and duration of surgical stimulus, aiming to achieve consistent and prolonged blunting of the hemodynamic and pain responses.

 

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Systemic Pharmacologic Agents and Their Limitations

Systemic agents—especially those administered intravenously—offer an alternative or adjunct to regional techniques. Alpha-2 agonists such as clonidine and dexmedetomidine have demonstrated efficacy in mitigating sympathetic responses due to their central sympatholytic effects. Clonidine, administered orally or intravenously, has been shown to reduce intraoperative anesthetic requirements and stabilize perioperative BP.[42] [57] [58] However, its side effects, particularly bradycardia and hypotension, necessitate careful dosing and patient selection.

Dexmedetomidine similarly exerts potent sympatholytic effects but is associated with a higher incidence of cardiovascular adverse events, particularly when administered as a bolus in standard doses (0.75–1 µg/kg).[3] [9] [54] In contrast, lower doses (e.g., 0.25 µg/kg), especially when combined with LA techniques, have demonstrated effectiveness without significant hemodynamic compromise.[12] [23] These findings suggest that lower-dose dexmedetomidine, in conjunction with regional anesthesia, may offer an optimal balance of efficacy and safety.

In contrast, opioids, once widely used for this purpose, have largely fallen out of favor due to inconsistent efficacy and the potential for side effects such as respiratory depression, delayed recovery, and tolerance. Most studies included in this review reported opioids as ineffective in adequately suppressing the hemodynamic response when used alone.

 

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Comparative Effectiveness and Clinical Implications

Notably, comparative studies between LA techniques and systemic agents suggest that both approaches are similarly effective when executed appropriately. However, systemic agents, particularly when administered in excessive doses or without careful timing, can provoke hypotension, a concerning complication in neurosurgical patients with altered autoregulation. Combining regional techniques with systemic agents at reduced dosages may offer synergistic benefits, enhancing efficacy while minimizing adverse effects.[7] [11] [12] [13] [14] [15] [17] [29] [55]

Agents such as gabapentin and magnesium have shown some promise, likely due to their central antinociceptive properties and modulation of calcium channels, though data remain limited. Conversely, β-blockers, benzodiazepines, and thiopentone have demonstrated minimal or inconsistent benefit in this context.

 

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Exploration of Nonpharmacologic Techniques

Interestingly, nonpharmacological approaches are also being explored. A pilot study involving sterile silicone studs to cushion the mechanical force of skull pins showed favorable outcomes in terms of hemodynamic stability compared with fentanyl.[59] While promising, these findings require validation in larger RCTs before clinical adoption.

 

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Limitations and Gaps in the Literature

While the reviewed evidence provides valuable insights, several limitations must be acknowledged. First, the studies reviewed did not uniformly assess the broader physiological stress response (e.g., pituitary hormone levels, catecholamine surge), which might provide a more comprehensive understanding of intervention efficacy.[60] Second, data on intracranial parameters such as ICP or CBF were largely absent. Third, the role of intraoperative anesthetic depth monitoring was underreported, despite its relevance in interpreting hemodynamic responses.

Furthermore, the type of skull pin used, such as Mayfield versus Sugita, was not consistently specified, though differences in design may influence pain perception and pressure distribution. Patient-specific factors, including preexisting hypertension and concomitant use of antihypertensive medications (e.g., β-blockers), were also not uniformly controlled for, potentially confounding the outcomes. Patient-specific factors such as age and underlying chronic illnesses significantly influence the physiological response and potential complications associated with skull pin insertion. In children, cerebral autoregulation is limited, making them more vulnerable to rapid hemodynamic fluctuations, which can compromise cerebral perfusion.[19] Conversely, elderly patients may have reduced cardiovascular reserve and a blunted compensatory response, increasing the risk of hypotension or bradycardia. Hypertensive patients are prone to an exaggerated sympathetic surge in response to noxious stimuli, potentially leading to abrupt increases in BP and HR, which can precipitate complications such as myocardial ischemia or intracranial hemorrhage.[61] Additionally, comorbidities like diabetes and autonomic dysfunction may further impair cardiovascular stability. These prognostic factors not only impact complication risk but may also affect the choice and efficacy of the anesthetic or pharmacological modality used, underscoring the importance of individualized approaches and the need for future studies to include subgroup analyses based on patient characteristics.

 

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Conclusion

Our systematic review found that among the evaluated techniques, SB and IV dexmedetomidine consistently demonstrated high effectiveness in attenuating the hemodynamic response to skull pin insertion. Clonidine also demonstrated reliable efficacy across multiple studies. LA infiltration was effective in the majority of cases but lacked uniform results, whereas opioids and β-blockers exhibited inconsistent or limited effectiveness. SB offers sustained coverage and greater flexibility but requires more skill and time, while pin-site infiltration is quicker and easier. Alpha-2 agonists like clonidine and dexmedetomidine are also effective, particularly when used in low doses (e.g., dexmedetomidine: 0.25 µg/kg), minimizing the risk of bradycardia and hypotension. Combining regional anesthesia with low-dose IV agents enhances efficacy and reduces side effects. Opioids alone are generally ineffective and should not be relied upon. Careful timing, dosing, and patient selection—especially in those with comorbidities—are essential. Depth of anesthesia monitoring may help optimize management. Nonpharmacologic methods like silicone pin cushions are promising but need further study. Future research should focus on standardizing techniques and comparing head pin types and anesthetic combinations to determine the safest and most effective approach.

 

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Conflict of Interest

None declared.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Authors' Contribution

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by C.K., P.L., and P.P. The first draft of the manuscript was written by C.K., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Publikationsverlauf

Artikel online veröffentlicht:
10. September 2025