|Year : 2022 | Volume
| Issue : 4 | Page : 309-315
Effect of scalp infiltration with bupivacaine on analgesic requirement following elective craniotomy
Abdulkareem A Abdullahi, Abdulrahman Aliyu
Department of Anaesthesiology and Intensive Care, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
|Date of Submission||28-Sep-2020|
|Date of Decision||14-Feb-2021|
|Date of Acceptance||17-Apr-2021|
|Date of Web Publication||16-Nov-2022|
Department of Anaesthesiology and Intensive Care, Usmanu Danfodiyo University Teaching Hospital, Sokoto
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Postcraniotomy pain and perioperative assessment of patients' neurological function are some of the issues associated with craniotomy surgeries. Cost-effective pain control will result in good clinical outcome, decrease the length of hospital stay, and reduce total cost. Infiltration anesthesia is a recognized modality of cost-effective pain control. Objective: The study determined the effect of scalp infiltration with 0.25% plain bupivacaine on pain control following craniotomy. Methods: A prospective randomized study recruited 50 consenting patients scheduled for craniotomy under general anesthesia into two study groups. All patients received routine general anesthesia as per local protocol and received scalp infiltration after skin closure. Group A received 20 ml of 0.25% plain bupivacaine, while Group B received 20 ml normal saline. Pain scores were assessed using the Visual Analog Scale (VAS) on admission into the intensive care unit (ICU) then at 4, 8, 12, 16, 20, 24, and 48 h after surgery. The interval between the end of surgery and the first request for analgesia, 4 hourly intervals pentazocine and the cumulative doses of pentazocine given for postoperative pain relief. Results: The presenting VAS at the ICU and total postoperative analgesic consumption at 48 h were significantly lower in the bupivacaine group compared to the saline group. In addition, the increase in time to the first analgesic request was statistically significant between the two. There was a trend toward the reduced incidence of sedation and postoperative nausea and vomiting in the bupivacaine group compared to the saline group. Conclusions: Postoperative scalp infiltration with plain 0.25% bupivacaine reduced pain intensity and opioid analgesic consumption among the studied patients. Resultantly, it can be regarded as an effective technique of pain management after an elective craniotomy.
| Abstract in French|| |
Contexte: La douleur post-craniotomie et l'évaluation périopératoire de la fonction neurologique des patients sont quelques-uns des problèmes associés aux chirurgies de craniotomie. Un contrôle de la douleur rentable se traduira par de bons résultats cliniques, réduira la durée du séjour à l'hôpital et réduira le coût total. L'anesthésie par infiltration est une modalité reconnue de contrôle de la douleur rentable. Objectif: L'étude a déterminé l'effet de l'infiltration du cuir chevelu avec de la bupivacaïne simple à 0,25 % sur le contrôle de la douleur après une craniotomie. Méthodes: Une étude prospective randomisée a recruté 50 patients consentants devant subir une craniotomie sous anesthésie générale en deux groupes d'étude. Tous les patients ont reçu une anesthésie générale de routine selon le protocole local et ont reçu une infiltration du cuir chevelu après la fermeture de la peau. Le groupe A a reçu 20 ml de bupivacaïne simple à 0,25%, tandis que le groupe B a reçu 20 ml de solution saline normale. Les scores de douleur ont été évalués à l'aide de l'échelle visuelle analogique (EVA) à l'admission en unité de soins intensifs (USI) puis à 4, 8, 12, 16, 20, 24 et 48 h après la chirurgie. L'intervalle entre la fin de la chirurgie et la première demande d'analgésie, les intervalles de quatre heures de Pentazocine ainsi que les doses cumulées de Pentazocine administrées pour le soulagement de la douleur postopératoire ont été enregistrés. Résultats: L'EVA présentée à l'USI et la consommation totale d'analgésique postopératoire à 48 h étaient significativement plus faibles dans le groupe bupivacaïne par rapport au groupe solution saline. De plus, l'augmentation du délai jusqu'à la première demande d'analgésique était statistiquement significative entre les deux. Il y avait une tendance à la réduction de l'incidence de la sédation et des nausées et vomissements postopératoires dans le groupe bupivacaïne par rapport au groupe solution saline. Conclusions: L'infiltration postopératoire du cuir chevelu avec de la bupivacaïne simple à 0,25 % a réduit l'intensité de la douleur et la consommation d'analgésiques opioïdes chez les patients étudiés. Par conséquent, elle peut être considérée comme une technique efficace de gestion de la douleur après une craniotomie élective.
Mots-clés: Analgésie, bupivacaïne, craniotomie, infiltration du cuir chevelu
Keywords: Analgesia, bupivacaine, craniotomy, scalp infiltration
|How to cite this article:|
Abdullahi AA, Aliyu A. Effect of scalp infiltration with bupivacaine on analgesic requirement following elective craniotomy. Ann Afr Med 2022;21:309-15
| Introduction|| |
Craniotomy is the surgical opening of the cranial cavity (cranium) and is generally thought to be less painful than other major operations such as thoracotomy or laparotomy. Postcraniotomy pain may be described as pulsating or pounding like in tension headaches or simply described as steady and continuous. The degree of postcraniotomy pain depends on the type of surgical approach; the base of the skull surgery is known to be associated with a higher incidence of disabling postoperative headache.
Postcraniotomy pain may be less severe compared to pain after other major operations, there is a growing consensus that it remains under-treated in the acute recovery phase.,, Poorly managed postcraniotomy pain may result in postcraniotomy headaches, reduced patient comfortability and poor quality of life after the surgery. In addition, patients' perioperative neurological assessment which is an important pivotal step at ensuring good clinical outcome after craniotomy may be challenging if the pain is not adequately treated. Intravenous analgesics such as opioids and nonsteroidal anti-inflammatory drugs are some of the routine pharmacological agents used in managing pain. These analgesics are often associated with adverse effects such as sedation, respiratory depression, analgesic nephropathy and increase risk of bleeding that may complicate surgical outcome.
A cost-effective pain control technique such as scalp infiltration will decrease the length of hospital stay, reduce treatment cost and result in good clinical outcome. The study determined the effect of scalp infiltration with 0.25% plain bupivacaine on pain control after craniotomy.
| Methods|| |
Following ethical clearance by the research and ethics committee of Usmanu Danfodiyo University Teaching Hospital, Sokoto, fifty patients were recruited into a prospective, randomized, double-blinded placebo-controlled study, performed between January 2012 and December 2013.
All patients with the American Society of Anesthesiologists (ASA) physical status class I-III, aged between 10 and 70 years who had elective craniotomy at Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria.
- Inability to understand, or incapacity to use the Visual Analogue Scale (VAS)
- Proven or suspected allergy to local anesthetics
- Patients chronically (>2 weeks) treated with narcotic medications
- Patients for emergency surgery
- Presence of headache.
The sample size of 22 patients in each group was determined based on the assumption that scalp infiltration will decrease the incidence of moderate to severe pain (VAS >4) by 50% (from 80% to 40%), with α of 0.05 and power of 80%. However, 25 patients per group were chosen to compensate for 10% attrition.
A total of 50 patients were recruited for the study and assigned into 2 groups of 25 each using a simple randomization method. Fifty sealed opaque envelopes were prepared, 25 of which were labeled letter “A” (bupivacaine group), while the remaining 25 were labeled letter “B” (saline group). These envelopes were presented to the patient for selection at each case by a research assistant until they were exhausted.
The day before surgery, appropriate patient selection and detailed preanesthetic evaluation were done with the study protocol explained to the patients. They were shown the VAS (a straight 10 cm line with 2 anchors) on which they were expected to place a line (perpendicular to) at the point that represented their pain intensity during the periodic postanesthetic pain assessment.
They all fasted for at least 6 h. Patients were also informed to demand analgesics when they are in pain. All patients received balanced general anesthetic with endotracheal intubation and mechanically controlled ventilation with close circuit system. Standard monitoring using pulse oximetry, noninvasive, and or invasive blood pressure, end-tidal carbon dioxide, electrocardiogram, temperature and urine output measurement, were applied throughout the procedures.
After premedication with intravenous midazolam 0.07 mg/kg (up to a maximum of 5 mg) at induction, patients were induced with fentanyl 0.5–1 mcg/kg, sodium thiopentone 3–5 mg/kg or propofol 2–2.5 mg/kg and atracurium 0.5 mg/kg to facilitate tracheal intubation. Other drugs given at induction, as indicated were dexamethasone and phenobarbitone. Prophylactic antibiotics (50 mg/kg IV Rocephin by Roche Pharmaceutical) were given to all the patients. Anesthesia was maintained with 100% oxygen in isoflurane, the end-tidal of which was kept at 0.25%–1%. Muscle relaxants and fentanyl were repeated as needed. There was no scalp infiltration with local anesthetics pre or intra-operatively. Intravenous mannitol, where indicated, was given before opening the dura.
The two solutions for scalp infiltration (20 ml of 0.25% plain bupivacaine; Duracaine brand by Alpha Pharm and Stores and 20 ml of 0.9% normal saline) were prepared and labeled in a 20 ml Agary inject syringes by the researcher. These were handed over to the research assistant who was also in custody of 50 sealed envelopes. The label on the corresponding solution was removed and handed over to the surgeon for infiltration at skin closure before the patient woke up with both surgeon and researcher being blinded to what the patient received. Patients in group A, received scalp infiltration with 20 ml of 0.25% plain bupivacaine, while those in group B received scalp infiltration with 20 ml normal saline. The solution not used for infiltration was discarded immediately by the research assistant without the knowledge of the researcher.
Following removal of the head holder, the isoflurane was discontinued; the residual effect of the muscle relaxant was reversed at the end of the surgery, oxygen flow was increased and the patients were allowed to recover from anesthesia. The patients' trachea was extubated when they were able to obey simple commands. An adequate neuromuscular reversal was evident by good hand grip and sustained head lift for >5 s.
When hemodynamic, respiratory, and neurologic evaluation were satisfactory, all the patients were transferred to the intensive care unit (ICU) with multiparameter monitoring (pulse oximetry, blood pressure and temperature), and oxygen supplement. Monitoring was continued in the ICU.
Postoperative pain was then assessed using the VAS on admission into the ICU, and thereafter four hourly for 24 h, later at 48 h after surgery by another anaesthetist also blinded to the study groups. The score was determined by measuring the distance on the line between the “no pain” anchor and the patient's mark providing a range of scores from 0 to 10. Intramuscular pentazocine (0.5–1 mg/kg of Fortwin by Ranbaxy Pharma) was given by the attending nurse, but only after the first request by the patient, thereafter every 4–6 h. Level of sedation, dysphoria, postoperative nausea and vomiting were equally assessed.
Data were collected by the use of a pro forma which contained demographic data as well as ASA physical status and site of surgery.
The following measurements and observations were made at the time of admission into ICU and thereafter at 4, 8, 12, 16, 20, 24, and 48 h after surgery; Pain scores with a 10 cm VAS as assessed by another anesthetist blinded to the study group were recorded (score of 0–0.4 = no pain, 0.5–3 = mild pain, 4–6 = moderate pain, and 7–10 = severe pain). Four hourly and cumulative doses of pentazocine given for postoperative pain relief were equally recorded. The time interval between the end of surgery (skin closure) and the first administration of pentazocine (time to first analgesic [TFA] request), assessments of sedation, postoperative nausea and vomiting carried out were documented. Nausea and vomiting was assessed using a categorical score (none = 0, nausea = 1 and vomiting = 2, nausea and vomiting = 3).
The level of sedation was assessed with the Ramsay sedation score below:
1 = Anxious/agitated
2 = Cooperative and calm
3 = Drowsy but responds to commands
4 = Asleep with brisk response to a stimulus
5 = Asleep with sluggish response to a stimulus
6 = Unarousable.
The undesirable effects were planned to be treated as follows: nausea and vomiting with intravenous metoclopramide 10 mg, sedation with respiratory depression (rate <10 cycles/min) from pentazocine administration with an incremental dose of naloxone intravenously, starting with 0.1 mg plus supplemental oxygen administration. Local anesthetic toxicity from direct intravenous injection was minimized and prevented by aspiration test before administration of the bupivacaine during the scalp infiltration. However, resuscitation drugs and equipment were made available both in the intraoperative and postoperative periods for airway maintenance and intravenous diazepam to treat a seizure.
Only data obtained from patients who were well oriented in person, place, and time and with a Glasgow coma score of 15 (at the time of assessment) were considered for statistical analysis.
Analysis of results
Statistical analysis of data collected was performed with the SPSS 17 was produced in 2008 before the acquisition by IBM hence given the origin as SPSS Inc. Results were expressed as the mean ± standard deviation except where stated otherwise.
Differences in demographic and postoperative data between the two groups were analyzed using the Chi-square test and unpaired Student's t-tests for nonparametric and parametric variables, respectively. Differences in VAS scoring between the two groups were evaluated with Student's t-tests. The TFA request, defined as the time interval between the end of surgery and the first administration of analgesic was analyzed with the unpaired Student's t-test after logarithmic transformation to ensure a normal distribution. A value of P < 0.05 was considered significant.
| Results|| |
Dermographic and surgical characteristics
[Table 1] shows the demographic profile of patients; mean age, sex and weight. The age range of the entire patients studied was between 19 and 51 years. The patients in both groups were comparable in age distribution, 33.12 (±10.83) years for bupivacaine group versus 35.52 (±8.59) years for the normal saline group, with a P value of 0.390.
|Table 1: Demographic and Surgical Characteristics in the Study and Control Groups|
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Sex distribution of the patients was comparable in both groups; 16 males (64%) and 9 females (36%) in bupivacaine group then 15 males (60%) and 10 females (40%) in saline group, P = 0.771.
The surgical site distribution shows 46 patients (92%) had supratentorial surgeries, [among whom 21 (45%) were in bupivacaine group and 25 (54.3%) are in saline group] whereas 4 patients (8%) had infratentorial surgery and were all in the bupivacaine group. P = 0.043
There was no statistically significant difference in the duration of surgery between the two groups, [202.56 (±34.20) minutes for bupivacaine group versus 199.20 (±27.14) minutes for the saline group, P = 0.70]. The time from the last fentanyl administration to skin closure [42.86 (±9.18) versus 45.78 (±8.04) minutes for bupivacaine and saline groups respectively, was also not significant, P = 0.091.
Pain intensity score
[Table 2] shows the VAS at the time of admission into ICU was significantly lower in bupivacaine group, with a mean score of 2.56 (±0.67) compared to 4.03 (±0.83) for the patients who had saline scalp infiltration; P value of 0.0001. All the patients in the bupivacaine group had VAS of <4 on admission into the ICU whereas only 36% of those in the saline group had that score with 64% having VAS >4. However, there was no statistically significant difference in VAS score at 4, 8, 12, 16, 20, 24, and at 48 h postoperatively because all the patients in the two groups were already receiving pentazocine.
|Table 2: Postoperative Visual Analogue Score in the Study and Control Groups|
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Postoperative analgesia requirement pattern
[Table 3] shows a statistically significant increase in the TFA request; in the bupivacaine group, it was 139.44 (±25.16) min, while in the normal saline group, it was 80.48 (±18.77), P = 0.0001.
|Table 3: Postoperative Analgesic Requirements In The Study And Control Groups|
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The four hourly interval pentazocine requirement among the two groups indicated a statistically significant reduction in patients who had bupivacaine scalp infiltration at 0–4 h (P = 0.0001) and 4–8 h (P = 0.008), however, it was not significant in both group patients at intervals of 8–12 h (P = 0.451), 12–16 h (P = 0.128), 16–20 h (P = 0.068), and 20–24 h (P = 0.565).
The table also shows the 48 h pentazocine requirement in both study and control groups. The bupivacaine group had a mean consumption of 208.80 (±16.16) mg compared to 242.40 (±19.21) mg in the saline group, with P = 0.0001.
The incidence and degree of sedation between the groups were found to be low at all the 5-time points observed, in the bupivacaine group (28%) compared to the saline group (44%), with Ramsay score of 3 on admission into ICU. No scores >3 or <2 were observed in both groups. The sedation score was however only significant (P = 0.01) at 4 h postoperative period [Table 4].
Postoperative nausea and vomiting
The incidence of nausea was found to be higher in the saline group, (16%) in the first 4 h postoperatively compared to the bupivacaine group (8%). No patient in the bupivacaine group reported vomiting, but 8% of those in the saline group had vomiting within the period. However, in the second 4-h assessment, there was an increased incidence of nausea in both studied groups (bupivacaine group 20%, saline group 32%). Twelve per cent (12%) of patients in each group vomited in the second 4 h period. There was no statistically significant difference in the incidence of PONV among both groups during the periods of assessment [Table 5].
|Table 5: Incidence Of Nausea And Vomiting In The Study And Control Groups|
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There were no complications such as arrhythmia, hypotension or convulsion recorded from the scalp infiltration (as a result of local anesthetic toxicity).
| Discussion|| |
This study showed that pain intensity was significantly lower in the bupivacaine group compared to the saline group where up to 64% of the patients in the saline group had moderate pain on admission into the ICU. This is evident from the TFA request in the bupivacaine group and the reduction in pentazocine consumption in the first few hours of the studied period compared to the saline group. However, there was no significant difference during the subsequently observed periods of 4 hourly pain assessments, because there was a progressive reduction in pain score in both groups as all the patients were receiving pentazocine within the period. The initial reduction in pain score in the bupivacaine group could be due to the action of bupivacaine used for infiltration in those patients. This is similar to the observation of De Benedittis et al. who documented 60% of craniotomy patients reporting moderate pain after craniotomy and also Quiney et al. who reported 60%–80% of post craniotomy pain to be moderate to severe or excruciating in the 1st postoperative h. Many factors such as gender (females experiencing pain more than males), race (whites having pain more than blacks), social class (high class more than low class) and culture are said to modify the perception of pain. Any of these factors, as well as observer differences, intraoperative analgesic protocol given to the patients in both groups and the study design, may have been responsible for the nonobservation of severe or excruciating pain in this study.
The study by Saringcarinkul and Boonsri demonstrated that scalp infiltration with 0.5% bupivacaine and adrenaline 1:400,000 decreased pain score and analgesic consumption but in the 1st h after supratentorial craniotomy. Similarly, in another study using 0.25% bupivacaine with adrenaline 1:200, 000 for wound infiltration reported a decrease in pain score after craniotomy for up to 1 h in postanesthesia care unit. The study by Law-Koune et al. and associate also demonstrated that scalp infiltration using 0.375% bupivacaine with adrenaline 1:200, 000, or 0.75% ropivacaine decreased postoperative pain score and morphine consumption but only for the first 2 h after surgery.
Our study demonstrated that scalp infiltration with 0.25% plain bupivacaine at skin closure decreased pain score and opioid analgesic consumption after craniotomy and this analgesia lasted up to a mean period of >2 h evident by the significant TFA requirement in the bupivacaine group. In contrast to the findings of the previous study, the observation of our study was surprising because a higher dose of bupivacaine was used compared to the present study but yet better and more prolonged analgesia was observed. This could be because the pain assessment in their study was done by different nurses on duty giving room for observer variability as opposed to a study where pain assessment was done by one Anaesthetist blinded to the studied groups. Another reason might be due to the timing chosen for the pain assessment in our study (0, 4, 8, 12, 16, 20, 24, and 48 h) compared to theirs (30 min, 1, 2, 4, 6, 8, and 12 h) which was more frequent allowing patients to be assessed when they were experiencing pain at those points of time. The different pain assessment scale used in the two studies could also be another factor as the correlation between the scales (VAS and numerical rating scale) for response options from “no pain” to “Unbearable pain” has been shown to range from 0.71 to 0.78 and 0.62 to 0.91, respectively.
The prolonged TFA requirement found in our study became significantly important as it allowed for early postoperative neurological assessment of the patients without the sedative effects of opioids. This finding was in keeping with the study by Biswas and Bithal who demonstrated that bupivacaine infiltration delayed analgesic requirement up to 2 h postoperatively.
In our study, there was also a statistically significant reduction in the mean cumulative pentazocine consumption in the bupivacaine group compared to patients in the saline group at the end of the study period of 48 h. This was because there was an initial reduction of pentazocine consumption in that group due to the effect of bupivacaine scalp infiltration. This was contrary to the findings by Saringcarinkul and Boonsri, who observed a reduction in the rescue analgesic consumption in the bupivacaine group only in the 1st postoperative h and not the cumulative analgesic doses. This is equally surprising but could have been due to their study design as patients were given tramadol based on a verbal numerical score of 4 or more, rather than patient request whereas in our study, patients were placed on a 4–6 hourly IM pentazocine for postoperative analgesia after the first request.
During the postoperative period, pentazocine was used as supplementary postoperative analgesia because it was readily available and has a relative safety index. It was also chosen based on the traditional regimen prescribed in the institution where the study was conducted. Some of the problems associated with intramuscular opioid dosing on demand include delay in timing between patient request and actual medication delivery, inadequate, unpredictable and fluctuating blood levels of the drug and lack of patient-specific titration of dose to effect., Although the inadequacy of intramuscular opioids prescribed on an as-needed basis for postoperative pain have been long recognized, the intramuscular route was used because it is the easiest, most convenient and relatively safe route of administration for the nursing staff. The use of pentazocine in this study has shown that the drug is effective in the management of postcraniotomy pain as observed in the pain intensity scores of patients in the studied groups. Apart from a slight delay in onset of action, IM pentazocine has a similar profile with Intravenous administration, but with fewer incidences of nausea and vomiting, sedation and respiratory depression and for these reasons, unwanted effects such as sedation, dysphoria, nausea, and vomiting were sought for in these studied patient groups.
There was a reduction in the incidence of sedation in the bupivacaine group compared to those in the saline group (20% vs. 68% Ramsay score 3 in the first 4 h with a P value of 0.01). This was an expected finding considering the reduced opioid requirement in this patient group and this has demonstrated one of the opioid-sparing effects of scalp infiltration with local anaesthetics when used for post craniotomy pain management. This finding was similar to those demonstrated in other studies.,,
There was no incidence of vomiting among patients who had bupivacaine scalp infiltration in the first 4 h postoperatively, but 2 patients (8%) had nausea, 2 (8%) patients in the saline group had an episode of vomiting and 16% had nausea. The incidence, however, increased in the subsequent interval time of assessment in the bupivacaine group, but statistically insignificant, with 12% of the patients having vomiting and 20% having nausea against 12% and 32%, respectively, in the saline group. This is not surprising as the observed period corresponded with the period of increasing opioid requirement in that group of patients. However, nausea and vomiting in both patients group subsided without the need for medication. Overall, there was a low incidence of nausea and vomiting in the studied groups, probably because of the administration of dexamethasone, a steroid with antiemetic properties, to the patients at induction. This is in keeping with the study by Bjorn et al., who reported 47% incidence of postoperative nausea and vomiting in post craniotomy period, but with a lower incidence in patients receiving steroid.
Limitations of the study
- One of the limitations of this study was the use of parenteral Pentazocin. Drug absorption from the intramuscular route of administration is erratic compared to the intravenous route
- The sample size used in this study may have reduced the power of the study to reflect the significance of scalp infiltration with bupivacaine in reducing analgesic requirement post craniotomy.
| Conclusions|| |
Scalp infiltration at skin closure, with plain bupivacaine 0.25% reduces postoperative analgesic consumption and is effective in improving pain management after craniotomy. In addition, the observed longer TFA request, less opioid requirement, lower pain intensity and reduced opioid-related adverse effects in this study indicate that better postoperative pain management can be achieved with this technique.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
De Benedettis G, Lorenzetti A, Spagnoli D, Migliore M, Tiberio F, Villani R. Postoperative pain in neurosurgery: a pilot study in brain surgery. Neurosurgery 1996;38:466-70.
De Gray LC, Matta BF. Acute and chronic pain following craniotomy: a review. Anaesthesia 2005;60:693-704.
Graham AC, Reid MM, Andrews PJ. Perception of pain experienced and adequacy of analgesia following craniotomy. Anaesthesia 1999;54:814-5.
Quiney NF, Cooper R, Stoneham MD, Walters F. Pain after craniotomy. A time for reappraisal? Brit J of Neurosurg 1996;10:295-9.
Saringcarinkul A, Boonsri S. Effect of scalp infiltration on postoperative pain relief in elective craniotomy with 0.5% bupivacaine with adrenaline 1:400,000. J Med Assoc Thai 2008;91:1518-23.
Huskinson EC. Measurement of pain. Lancet 1994;2:1127-31.
Shende D, Sadhasivam S, Madan R. Effect of peribulbar bupivacaine as an adjunct to general anaesthesia on peri-operative outcome following retinal detachment surgery. Anaesthesia 2000;55:970-5.
Liu LL, Gropper MA. Postoperative analgesia and sedation in adult intensive care. A guide to drug sedation. Drugs 2003;63:755-67.
Law-Koune JD, Szekely B, Boudreaut D, Fugere F, Ruel M, Moumdjian R, et al. Scalp infiltration with bupivacaine plus epinephrine or plain ropivacaine reduces postoperative pain after supratentorial craniotomy. J. Neurosurg Anesthesiol 2005;17:139-143.
Biswas BK, Bithal PK. Preincision 0.25% Bupivacaine scalp infiltration and post craniotomy Pain; A Randomized Double-Blind, Placebo-Controlled Study. J. Neurosurg. Anesthesiol 2003;15:234-9.
Henderson K. Pentazocine. Update in Anaesthesia 2008;24:8-12.
Paddock R, Bee EG, Belville JW, Benjamin JC, William HF, Elliot VM. Analgesia and side effects of pentazocine and morphine in a large population of postoperative patients. Clinical Pharmacology and Therapeutics 1969;10:355-65.
Kehlet H, Rung GW, Callesen T. Postoperative opioid analgesia: Time for a Reconsideration? J Clin Anesth 1996;8:441-5.
Bjorn L, Mordhorst C, Thomas K, Annette S, Gregor W, Christian W, et al. Postoperative nausea and vomiting in patients after craniotomy: incidence and risk factors. J Neurosurg 2011;114:491-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]