|Year : 2007 | Volume
| Issue : 3 | Page : 211-215
Effect of propofol and thiopentone on intracranial pressure and cerebral perfusion pressure in patients undergoing elective craniotomy - a comparative study
Sankari Santra1, Bibhukalyani Das2
1 M.D., Asst. Professor, Department of Neuroanaesthesiology, Neuro ICU and Pain Clinic, Bangur Institute of Neurology, I.P.G.M.E. & R., Kolkata, India
2 M.D., Professor and HOD, Department of Neuroanaesthesiology, Neuro ICU and Pain Clinic, Bangur Institute of Neurology, I.P.G.M.E. & R., Kolkata, India
|Date of Acceptance||10-Mar-2007|
|Date of Web Publication||20-Mar-2010|
142, Rubypark East, Kolkata - 700078
Source of Support: None, Conflict of Interest: None
Advantages and disadvantages of newer agent like propofol need to be evaluated with time tested inducing drug - thiopentone in neuroanaesthesia. The aim of the study was to compare effects of propofol with thiopentone on intracranial pressure, cerebral perfusion pressure and haemodynamics during induction in neurosurgical patients. Fifty adult patients of ASA grade I& II scheduled for elective craniotomy were randomly assigned to receive induction of anaesthesia with either propofol 1.5-2.5 mg.kg -1 i.v. (Group A, n=25) or thiopentone 4-5 mg.kg -1 , i.v. (Group B, n=25). Vecuronium bromide 0.1 mg.kg -1 i.v. was used as intubating muscle relaxant. Both groups received fentanyl 2 pg.kg -1 i.v., lidocaine(preservative free) 1.5 mg.kg -1 i.v. and supplementary dose of same inducing agent before intubation. Changes in mean arterial pressure (MAP), cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure (CPP) and heart rate (HR) were noted during induction and endotracheal intubation. On statistical analysis it was found that CSFP decreased significantly (P<0.001) in both groups after induction but endotracheal intubation did not provoke any significant rise in CSFP. Maximum decrease of CSFP was 35.26% in Group A and 35.20% in Group B. Fall in MAP was more significant in Group A (P<0.001), as a result CPP was significantly less in Group A than in Group B. The lowest mean CPP (71.12±5.86 mm Hg) was observed 2 minutes after induction dose in Group A when maximum drop in MAP occurred. Heart rate did not change significantly in Group A but in Group B fluctuation of heart rate was more.
Keywords: Propofol, Thiopentone; Intracranial pressure; Mean arterial pressure; Cerebral perfusion pressure; Elective craniotomy.
|How to cite this article:|
Santra S, Das B. Effect of propofol and thiopentone on intracranial pressure and cerebral perfusion pressure in patients undergoing elective craniotomy - a comparative study. Indian J Anaesth 2007;51:211-5
|How to cite this URL:|
Santra S, Das B. Effect of propofol and thiopentone on intracranial pressure and cerebral perfusion pressure in patients undergoing elective craniotomy - a comparative study. Indian J Anaesth [serial online] 2007 [cited 2020 Jan 28];51:211-5. Available from: http://www.ijaweb.org/text.asp?2007/51/3/211/61144
| Introduction|| |
The patients having intracranial pathology especially space occupying lesions in brain are usually in a state of delicate intracranial homeostasis. Maintenance of an optimal cerebral perfusion pressure is a key factor in managing these patients during perioperative period. Induction of anaesthesia, laryngoscopy and endotracheal intubation may produce deleterious effects on mean arterial pressure (MAP), intracranial pressure (ICP)& therefore on cerebral perfusion pressure (CPP). The control and manipulation of cerebral blood flow (CBF) are central to the management of ICP during anaesthesia because CBF varies according to vasoconstrictor - vasodilator response of anaesthetic agent.
Thiopentone causes dose dependent depression of cerebral metabolic rate of oxygen (CMRO 2 ). In addition there is parallel reduction in CBF& ICP. ICP is decreased proportionally more than MAP. Therefore CPP remains un-compromised. This is particularly beneficial for patients with increased ICP making thiopentone an appropriate drug during induction of anaesthesia in neurosurgery. 
Most studies have shown that propofol either decreases or does not change ICP. , At the same time MAP is decreased by almost in same magnitude or more. Thus CPP is decreased in most circumstances. However Ravussin P et al found that lumbar CSF pressure during induction with propofol decreased by 32%& MAP decreased by 10%. . Considering the results of previous studies, the aim of this study was to evaluate propofol as an inducing agent in comparison to thiopentone - the well established inducing agent in neurosurgical patients.
| Methods|| |
This study was carried out in the Dept. of Anaesthesiology, at Bangur Institute of Neurology, IPGME& R, Kolkata. After obtaining permission from Ethical Committee fifty adult ASA grade I& II patients, aged 2060 years, of either sex, scheduled to undergo elective craniotomy were enrolled in this study.
Exclusion criteria -
Patients were randomly allocated in two groups. Group A was propofol group and comprised of 25 patients, Group B was thiopentone group which also comprised of 25 patients.
- Intracranial pathology obstructing cerebro-spinal fluid (CSF) pathways between lateral ventricles& lumbar CSF space.
- Any intraventricular drain or ventriculo-peritoneal shunt already in place.
- Patients having significant cardio vascular, respiratory, hepatic or renal disease.
- Allergy to study drugs.
All patients were premedicated with midazolam 0.1 mg.kg -1 body weight intramuscularly 1 hour prior to induction of anaesthesia. Before induction a 20 gauge catheter was inserted into the radial artery to record mean arterial pressure (MAP). With full aseptic technique a 20 gauge malleable catheter (Perifix, B'Braun) was placed in lumbar subarachnoid place. Utmost precaution was taken not to drain any cerebrospinal fluid (CSF).
MAP and cerebrospinal fluid pressure (CSFP) were measured in supine position using previously calibrated Hewlett Packard 1290C pressure transducer referred to the lateral midthoracic line and external auditory meatus respectively. Mean pressures were determined by electronic integration of the respective transducer signals using a multichannel M1205A Hewlett Packard system.
All patients were pre-oxygenated with 100% oxygen for 3 minutes. Induction was done with sleep dose of propofol (1.5 - 2.5 mg.kg -1) i.v. in Group A and thiopentone (4 - 5 mg.kg -1) i.v. in Group B. Induction was considered successful when there was no response to verbal commands and loss of eyelash reflex. Vecuronium bromide 0.1 mg.kg -1 i.v. was then administered to facilitate tracheal intubation. Fentanyl 2 gg.kg -1 i.v. was administered at the same time. Ventilation was assisted by intermittent positive pressure with the help of face mask. Trachea was intubated 3 minutes after administering vecuronium bromide. Lidocaine 1.5 mg.kg -1 i.v. was injected in each group 90 seconds before intubation. Each group received a supplementary dose of 30% required inducing dose of same inducing agent 1 minute prior to intubation. Anaesthesia was maintained with 66% nitrous oxide in oxygen and supplemented with 0.8% isoflurane. Hypoxia was avoided and normocarbia was maintained throughout the procedure.
MAP, CSFP, CPP (MAP - CSFP), HR were all measured, derived before induction, 1 minute, 2 minutes, 3 minutes after induction and 1 minute, 2 minutes and 5 minutes after endotracheal intubation. Student's paired 't' test with correction for multiple comparison and two sample 't' test were used for statistical analysis.
| Results|| |
The study groups were comparable with respect to age, sex, body weight and distribution of clinical diagnosis [Table 1]. The induction doses of thiopentone and propofol were 4.8±0.7 mg.kg -1 and 2.2 ±0.4 mg.kg -1 respectively. The mean induction time was 36 seconds in Group A and 33 seconds in Group B.
[Table 2] shows the CSFP, MAP and CPP values during the study in both the groups. CSFP decreased after induction in both the groups. Both the agents caused a maximal decrease in CSFP of 35.26% which occurred at 2 minutes after induction in Group A and 35.20% occurred 3 minutes after induction in Group B. Intubation increased CSFP in both the groups. Post intubation CSFP, however remained lower than the baseline CSFP in both the groups. The magnitude of CSFP increase was not different between the groups.
CPP (MAP - CSFP) decreased significantly and remained lower than the baseline value up to 1 minute before intubation in Group A. A statistically significant decrease in CPP occurred only at 2 minutes after induction in the Group A. Intubation increased the CPP in both the groups. The increase was however, statistically significant only in Group B at the time of intubation and 1 minute after intubation. At 2 minute after induction and at the time of intubation, Group B had a significantly higher CPP because of comparatively higher MAP than Group A.
Heart rate did not change significantly in Group A throughout the study period. In contrast, HR fluctuated more in Group B. However, most significant increase (from 72.84 ± 12.55 to 89.65 ± 13.51 P, <0.001) occurred in Group B during intubation.
| Discussion|| |
In neuroanaesthesia, considerable emphasis is placed on the manner in which anaesthetic agents and techniques influence CBF and cerebral blood volume (CBV) ,. Changes in CBF, so also CBV is the prime determinant of ICP changes during anaesthesia in patients having intracranial space occupying lesions. Cerebral autoregulation normally serves to prevent MAP related increase in CBV. In fact, as the cerebral circulation constricts to maintain a constant CBF in the face of a rising MAP, CBV actually decreases . But in patients with intracranial space occupying lesion, autoregulation usually remains impaired. When autoregulation is impaired or the upper limit (~ 150 mmHg) is exceeded, CBF and eventually CBV increase in parallel to arterial pressure rise. Subsequently a declining MAP causes cerebral vasodilatation to maintain a constant flow resulting in progressive increase in CBV. Thus exaggerated increase in CBV occurs as MAP falls below the lower limit of autoregulation. This increase in CBV in the face of falling MAP is the principal reason for ICP increase. In healthy subjects initial increase in CBV does not result in significant ICP elevation because there is latitude for compensatory adjustment by other intracranial compartments. After exhaustion of compensatory adjustment, reduction in intracranial compliance occurs and further increase in CBV can cause brain herniation or may reduce CPP sufficiently to cause ischaemia.
There have been several investigations related to the effects of anaesthetic agents on CBV in normal brain ,. Intravenous anaesthetics in general, cause a decrease in CBF and CMRO 2. The decrease in CBF induced by most of the intravenous anaesthetics appears to be the result of decreased cerebral metabolism secondary to cerebral functional depression.
Thiopentone produces a dose dependent reduction in CBF and CMRO 2 until the EEG becomes flat. At the point of isoelectrical EEG, no further CMRO 2 reduction occurs despite of further increase in barbiturate dose . The maximal thiopentone induced CMRO 2 decrease is 55 to 60%. Thus with barbiturates, functional depression appears to be coupled with reduction in CBF and CMRO 2. ICP is reduced by barbiturates, possibly because of reduction in CBF& CBV. This effect is used during the treatment of raised ICP in head injured patient as well as induction of anaesthesia in patients with decreased intracranial compliance.
The haemodynamic effect of propofol on induction have been reported in detail and compared with other agents ,,. Most studies have shown that propofol either decreases or does not change ICP ,,,. In this study induction dose of propofol decreases CSF pressure up to 35.26%.
Experimental analysis has revealed that an intracranial - cisterna magna pressure gradient will develop only when the lateral ventricular pressure is above 20 mmHg . In this study all patients were clinically free of pathology judged likely to obstruct the pathways of CSF between the intracranial and lumbar spaces. So we measured lumbar CSFP as a close and accurate reflection of lateral ventricular pressure.
This study demonstrated that anaesthetic induction using propofol produces a decrease in CSFP similar in magnitude and duration to that found with thiopentone. CSFP changes during induction and endotracheal intubation in both groups are shown in [Table 2] at different time interval. CSF pressure decreased significantly after induction dose of propofol or thiopentone. Maximum drop occured 2 minutes after induction in propofol group which is similar to the results of previous studies ,.
Propofol produced a larger decrease in CPP, 2 minutes following induction when compared to thiopentone. This was not surprising as propofol has been shown previously to cause a 15-30% decrease in MAP during induction because of variable decrease in systemic vascular resistance and cardiac output ,. In our study, though CPP was lower in propofol group than thiopentone group, it was never decreased below 70 mmHg. This is in contrast to administration of large dose of propofol which have been clearly demonstrated in earlier reports to decrease the CPP to less than 50mmHg  - a value below the lower limit of cerebral autoregulation at which reduction in CBF will occur. But we administered propofol slowly until loss of eyelid reflex was achieved, a method of induction previously shown to conserve CPP above 70mmHg and to leave HR unchanged. Similarly to the findings of Doze et al ,, in our study, propofol more effectively attenuated the MAP response to laryngoscopy and tracheal intubation when compared to thiopentone. This produced a smaller increase in CPP in propofol group during intubation as there was no difference in the CSFP increase between two groups.
Heart rate changes were also small in magnitude in propofol group (P>0.05) but significant (P<0.001) in thiopentone group during intubation. The better control of heart rate with propofol may be due to a greater depth of anaesthesia  or lack of any antanalgesic effect  or propofol per se induces minimal changes in heart rate because resetting of baroreceptor reflex.
Hartung HJ  reported no change in CSFP after low dose of propofol (1 mg.kg -1) in patients with head injuries. Recent investigations in primates and humans indicate that propofol produces a dose dependent decrease in CBF and to a lesser extent CMRO2 ,. This is in contrast to the coupled decrease in CBF and CMRO 2 that is well established for thiopentone. This may raise some concern that propofol may decrease CBF more than cerebral O 2 demand, although this decoupling of CBF from CMRO 2 may have been related to the level of anaesthesia at the time of CBF measurement  .
From the observations and results of this study, it can be concluded that propofol is a reasonable alternative to thiopentone during induction of anaesthesia in patients with intracranial pathology, provided careful dose titration is done to maintain CPP within the range of autoregulation.
| References|| |
|1.||Albrecht RF, Miletich DJ, Rosenberg R, et al. Cerebral blood flow& metabolic changes from induction to onset of anesthesia with halothane& pentobarbital. Anesthesiology 1977; 47:252-256. |
|2.||Hartung HJ. Intracranial pressure after propofol and thiopentone administration in patients with severe head trauma. Anaesthetist 1987; 36:285-287. |
|3.||Ravussin P, Guinar JP. Ralley F, et al. Effect of propofol on cerebrospinal fluid pressure and cerebral perfusion pressure in patients undergoing craniotomy. Anaesthesia 1988; 43(suppl.):37-41. |
|4.||Todd MM, Weeks J. Comparative effects of propofol, pentobarbital& isoflurane on cerebral blood flow& blood volume. J neurosurg Anesthesiol 1996; 8:296-303. |
|5.||Stuliken EH, Milde JH, Michenfelder Jd, et al. The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane& thiopental. Anesthesiology 1977; 46:28-34. |
|6.||Ferrari M, Wilson DA, Hanley DF, et al. Effect of graded hypotension on cerebral blood flow, blood volume& mean transit time in dogs. Am J Physiol 1992; 262: 1908-14. |
|7.||Artru AA. Dose related changes in the rate of cerebrospinal fluid formation& resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam& etomidate in dogs. Anesthesiology 1988; 69 : 541-546. |
|8.||Artru AA, Shapira Y, Bowdle TA . Electroencephalogram, cerebral metabolic& vascular responses to propofol anesthesia in dogs. J Neurosurg Anesthesiol 1992; 4 : 110-119. |
|9.||Steen PA, Newberg L, Milde JH, et al. Hypothermia and barbiturates individual& combined effects on canine cerebral oxygen consumption. Anesthesiology 1983; 58 : 527-532. |
|10.||Ravussin P, Temple Hoff R., Modica PA, et al. Propofol Vs. thiopental- isoflurane for neurosurgical anesthesia. Comparison of hemodynamics CSF pressure and recovery. Journal of Neurosurg Anesthesiol 1991; 3: 85-95. |
|11.||VandesteeneA, Trempont V, Engelman E, et al. Effect of propofol on cerebral blood flow and metabolism in man.Anaesthesia 1988; 43 (suppl.) ; 42-43. |
|12.||Doze VA, Shafer A. White PF. Propofol-nitrous oxide versus thiopental-isoflurane-nitrous oxide for general anesthesia. Anesthesiology 1988; 69:63-71. |
|13.||Takizwa H, Gabra Sanders T, Miller JD. Analysis of changes in intracranial pressure and pressure volume index at different location in the cranio-spinal axis during supratentorial balloon inflation. Neurosurgery 1986; 19 : 1-8. |
|14.||Van - Hemelrijik J, Van Aken H, Plets C, et al. The effects of propofol on intracranial pressure and cerebral perfusion pressure in patients with brain tumors. Acta Anaesthesial Belg 1989; 40 : 95-100. |
|15.||Stephan H, Sonntag H, Schenk HD, Kettler D, Khambatta HJ. Effects of propofol on cardiovascular dynamics, myocardial blood flow and myocardial metabolism in patients with coronary artery disease Br J Anaesth 1986; 58:969-975. |
|16.||Coats DP, Monk CR. Prys-Roberts C, Turtle M. Hemodynamic effects of infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesth Analg 1987;66:64-70. |
|17.||Doze VA, Westphal LM. White PF. Comparison of propofol with other methods for outpatient anesthesia. Anesth Analg 1986; 65:1189-1195. |
|18.||Fahy LT, Van Mourik GA, Utting JE. A Comparison of the induction characteristics of thiopentone& propofol (2, 6-diisopropyl phenol). Anaesthesia 1985; 40: 939-944. |
|19.||Van Hemelrijck J, Fitch W, Mattheussen M, Van Aken H, Plets C, Lauwers T. Effects of propofol on cerebral circulation and autoregulation in the baboon. Anesth Analg 1990; 71:49-54. |
[Table 1], [Table 2]