Factors Affecting Time to Emergence From General Anesthesia Following Clipping of Ruptured Aneurysms: A Prospective Observational Study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.329619
Source of Support: None, Conflict of Interest: None
Keywords: Aneurysmal SAH, emergence, postoperative
The incidence of major complications after an intracranial surgery has been reported in 13% to 27% of patients. Consequently, it is desirable to have an awake patient at the end of neurosurgery for immediate neurological evaluation and detection of any postoperative cerebral complication. Besides the feasibility of neuromonitoring among patients who wake up early, they have fewer hemodynamic and metabolic consequences when compared to those with delayed awakening. The incidence of early extubation in neurosurgical patients who undergo intracranial surgery is around 82% to 89%.,
Subarachnoid hemorrhage (SAH) is a disease with high mortality and morbidity, causing immense psychosocioeconomic burden., Among the various causes of subarachnoid hemorrhage, ruptured aneurysms constitute the most frequent cause, with surgical clipping continuing to play an essential role in management. An elective neurosurgical patient has well-compensated intracranial pathophysiology. However, in patients with intracranial SAH who suffer acute neurological insults, there is a sudden rise in intracranial pressure (ICP), and the compensatory mechanisms may be insufficient leading to neuroinflammation and cerebral ischemia.,, Subjecting these patients to anesthesia and neurosurgery may add to the neurological insults and affect the emergence from anesthesia.
The present study was designed to prospectively evaluate the time to awakening in patients undergoing clipping of aneurysmal neck following SAH. The study also aims to evaluate the effect of various preoperative and intraoperative factors on the time to emergence in these group of patients.
The study was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, over a period of one and a half years. Following approval from the institutional ethical committee, the study was conducted in 67 patients aged 20–65 years, with American Society of Anesthesiologists (ASA) Grades I–III, and World Federation of Neurosurgical Societies (WFNS) Grades I–III, undergoing clipping of ruptured aneurysms. Written informed consent was taken from all the patients or next of their kin. Since it was an observational study, the protocol for the management of anesthesia was left to the discretion of the attending anesthesiologist. The intraoperative monitoring included 5-lead continuous electrocardiography, heart rate, invasive blood pressure, pulse oximetry, end tidal CO2, temperature, and urine output.
Demographic data including age, sex, and weight were recorded in all the patients. The preoperative data also included ASA physical status, Glasgow Coma Score (GCS), WFNS, grade and Fisher grade.
Total anesthetic time, total surgical time, estimated total intraoperative blood loss, amount of intravenous fluids administered, urine output, temporary clipping time, intraoperative aneurysmal rupture, body temperature at the end of the surgery (≤36 or >36°C), and use of anesthetic drugs were recorded.
Following completion of surgery and discontinuation of anesthesia, the residual neuromuscular blockade was reversed. The patients were observed for awakening from anesthesia and response to verbal commands. The time to awakening was defined as the time from discontinuation of anesthetic agent to the patient's response to verbal commands. The decision of tracheal extubation following cessation of anesthesia was at the discretion of the attending anesthesiologist in consultation with the neurosurgeon. The patients were extubated if (1) they were hemodynamically stable; (2) there was an adequate reversal of neuromuscular blockade; (3) there was return of spontaneous and regular respiration with appropriate tidal volume; (4) there was ability to maintain proper oxygen saturation; and (5) there was spontaneous eye-opening or response to verbal commands. When the patients could not be extubated in the operation theater, the patients were shifted to neurosurgical intensive care units for ventilator support.
Sample size calculation
The sample size was based on the study period. The study was conducted between July 2013 and December 2014. All patients were prospectively screened during this period for inclusion and exclusion criteria. Those patients who met the inclusion criteria were enrolled in this study.
SPSS 21 software (IBM Corp., New York, USA) was used for the statistical analyses. After evaluating for normality of data, nonparametric tests were chosen. Univariate analyses of continuous variables utilized Mann–Whitney U test across binary categories and Kruskal–Wallis test across multiple categories. The bivariate relationship between two continuous variables was assessed using Spearman's rank-order correlation coefficient. Multivariate analysis was conducted using generalized linear model (gamma distribution) for evaluating time to emergence with the mandatory significance of the model coefficient being <0.05, after adjusting for other known prognostic factors such as age, ASA grade, Fisher grade, preinduction GCS, duration of temporary clipping, duration of anesthesia, and patient's temperature at the end of surgery.
A total of 70 patients were screened for the study, of which 69 patients met the inclusion criteria. Two patients died on the second postoperative day and thus were excluded from the study. Consequently, a total of 67 patients were considered for the final analysis. The median age was of the patients was 46 years (interquartile range [IQR] = 40–53]. Thirty-three males and 34 females were included in the study. The median weight of the patients was 64 kg (IQR = 58–68). Forty patients were of ASA Grade I and 26 patients were of ASA Grade II, whereas only one patient belonged to ASA Grade III. Ten patients in the early awakening group and 19 patients in the delayed awakening group had sinus bradycardia, ST-T wave abnormalities and left ventricular hypertrophy. However, there is no significant difference between the two groups when cardiac changes were considered (P = 0.37). Forty, 16, and two patients were of WFNS Grades I, II, and III, respectively, at the time of admission. The number of patients with admission computed tomography Fisher Grades I, II, III, and IV were six, 20, 25, and 16, respectively.
Of the 67 ruptured aneurysms, 29 were in the anterior communicating artery (ACOM), 20 in the middle cerebral artery, eight in the internal carotid artery (ICA; three ICA bifurcation, two posterior communicating artery, one posterior cerebral artery, one anterior choroidal artery, one carotico-ophthalmic segment), and two in the distal anterior cerebral artery, and seven had multiple artery aneurysms. Out of the 67 patients with ruptured aneurysms, four patients had evidence of vasospasm on preoperative cerebral angiography. The duration from the ictus to the day of the surgery was 3 days (IQR = 1–7 days). Sixty patients had GCS 15, six had GCS of 14, whereas one patient had GCS 13 prior to induction of anesthesia.
Preoperative blood investigations such as hemogram, coagulogram, renal functions, random blood sugar, and serum electrolytes were comparable in both groups of awakening. Special consideration was given to serum electrolytes as dyselectrolytemia (mainly hyponatremia) is one of the crucial causes of delayed awakening. Average serum sodium levels in the early and late awakening group were 138.09 ± 4.3 and 141 ± 5.2, respectively, with no statistical significance (P = 0.34). Similarly, serum potassium and chloride levels were also similar.
Anesthesia was induced with thiopentone and propofol in 17 and 50 patients, respectively. Fifty-five patients received intravenous morphine, whereas 12 patients received fentanyl for intraoperative analgesia. Anesthesia was maintained with isoflurane, propofol, and desflurane in 38, 22, and seven patients, respectively. During bone flap elevation 23, 31, 10, and three patients had Grades I, II, III, and IV brain relaxation scores, respectively. At the time of the craniotomy closure 45, 21, and 1 patient had Grades I, II, and III brain relaxation scores, respectively. There was no statistically significant correlation between brain relaxation during bone flap elevation and craniotomy closure with respect to time to awakening. Normal saline was used as the maintenance fluid in all the patients (3.5 L, IQR = 3–4 L). Blood loss was found to be within the range of maximum allowable blood loss in all the patients (400 mL, IQR = 300–500 mL). The duration of temporary clipping was 3.5 (IQR = 2–6.67) minutes. Four patients had intraoperative aneurysm rupture. The duration of anesthesia and surgery were 230 (IQR = 190–310) and 180 (IQR = 140–265) minutes, respectively. The median time to emergence was 17 (IQR = 10–240) minutes.
On univariate analysis, the factors that were found to have significant correlation with time to emergence were preinduction GCS (P = 0.002), WFNS grade (P = 0.005), temporary clipping time (P = 0.03, ρ = 0.26) and the temperature at the end of the surgery (P < 0.001, ρ = -0.55).
The median time to emergence with GCS 13, 14, and 15 were 720, 480 (IQR = 22–1,680), and 14.5 (IQR = 10–120) minutes, respectively. A significant difference in emergence time across the different preinduction GCS score was found (P = 0.01) [Figure 1].
The median time to emergence in Fisher Grades 1–3 was 15.0 (IQR = 10–30), compared with 180.0 (IQR = 12–540) minutes in Fisher Grade 4 (P = 0.12). No significant association was found with Hunt and Hess and time to emergence [Figure 2]. A total of three patients in the study had intraventricular hemorrhage and hydrocephalus (HCP), out of which two patients had delayed awakening, but it was not statistically significant.
A significant rank-order correlation between temporary clipping (TC) duration and time to emergence was found (P = 0.03, ρ = 0.26) The median time for TC was 3.5 (IQR = 2–6.67) minutes [Figure 3].
The median temperature at the end of the surgery was 35.8°C (35.4°C–36.2°C). A significant correlation with temperature at the end of the surgery and time to emergence was found (P < 0.001, ρ = -0.55) [Figure 4] depicts a negative rank-order correlation between temperature and the time to emergence at the end of the surgery.
There was no effect of the choice of the anesthetic agents (P = 0.34) or opioids (P = 0.13) on the time to emergence. There was no correlation with brain bulge at the time of flap elevation (P = 0.27) and dural closure (P = 0.29) with the emergence following surgery. None of the other preoperative and intraoperative factors were found to have any statistically significant correlation with time to emergence in patients undergoing surgery for aneurysmal clipping.
In generalized linear model (γ-distribution), preinduction GCS (P < 0.001), patient's temperature at the end of surgery (P < 0.001), and TC duration (P = 0.01) had significant impact on the emergence time, independent of age, ASA grade, Fisher grade, duration of anesthesia and of each other, in the order of magnitude, with GCS and temperature having the maximum impact [Table 1].
The neurological status of patients with SAH is determined by the ongoing pathophysiological mechanisms of vasospasm and inflammation, closely linked with the properties of anesthetic agents and awakening.,, Awakening remains a challenge in patients undergoing neurosurgery as both anesthesia and surgery affect the brain. Emergence in neurosurgical patients is dependent on multiple factors that include the preoperative neurological status of the patient and intraoperative surgical and anesthetic factors. Early awakening, though desirable, may be delayed in case of prolonged surgery (usually more than 6 hours), surgery for large tumors or resection of arteriovenous malformations, massive intraoperative bleeding, poor preoperative level of consciousness, and in patients with severe cardiac or respiratory impairment. Emergence from anesthesia has been widely studied in patients undergoing elective surgery who have well-compensated intracranial physiology. However, the influence of various perioperative factors that can affect awakening in patients with acute neurological insults needs to be understood. The present study analyzed the factors that could influence awakening in patients undergoing surgery following aneurysmal SAH. Preinduction GCS, patient temperature at the end of the surgery, Fisher grade, duration of TC, and duration of anesthesia had significant impact on the emergence time in patients undergoing clipping for ruptured aneurysm. None of the other preoperative and intraoperative factors had any impact on time to emergence in the patients undergoing clipping of aneurysmal neck.
In this study, the anesthesia technique with respect to opioids and hypnotic agents did not have an impact on emergence and brain conditions. Various anesthetic agents were compared to assess their effect on brain conditions and awakening in elective supratentorial craniotomies. Dube et al. compared sevoflurane and desflurane, whereas Bastola et al. compared propofol, desflurane, and sevoflurane. Both groups of authors found comparable brain relaxation scores and postoperative recovery with different agents. Bhagat et al. compared morphine and fentanyl for emergence following supratentorial craniotomy and found that morphine was similar to fentanyl for facilitating emergence. There is traditional prejudice against the use of opioids in neurosurgical patients that morphine is associated with delayed recovery compared with fentanyl. Bhardwaj et al. carried out randomized clinical trial comparing propofol and desflurane in aneurysmal surgery. They found that both the agents were similar in terms of intraoperative hemodynamics, brain relaxation, time to eye-opening, response to verbal commands, and extubation time (P > 0.05).
The median time to emergence from anesthesia in our study was 17 minutes. The mean emergence time in patients undergoing elective craniotomy for supratentorial tumors varied from 4 minutes to 10 minutes in various studies.,, The difference in the awakening time in our study could be due to the emergent nature of surgery in a patient population where there is an acute neurological insult due to sudden rise in ICP and exhaustion of intracranial compensatory mechanisms. The patients undergoing elective tumor surgery have well-compensated intracranial physiology, which may result in early awakening following general anesthesia when compared with patients being subjected to craniotomy following aneurysmal SAH.
In our study, the preinduction GCS was found to significantly correlate with time to emergence following aneurysm neck clipping following SAH. The patients with preinduction GCS of 15 were awake within 15 minutes following anesthesia, whereas those who had preoperative GCS of 14 woke up at a median time of 8 hours. The overwhelming difference in emergence time with single-point reduction in GCS emphasizes its importance as a reflection of ongoing intracranial pathophysiology in patients with aneurysmal SAH. Nivatpumin et al. found GCS less than 13 as an independent predictor of delayed extubation (extubation more than 6 hours after the surgery). Few authors found GCS less than 8 to be significantly associated with extubation failure (need of reintubation within 24–72 hours) in neurosurgical patients., In a multivariate analysis, the success of extubation has been reported to be 75% in patients who had higher GCS, whereas it was 33% in those with lower GCS. With each incremental improvement in the GCS, the odds ratio of successful extubation has been observed to increase by 39%. It is important to note that only the patients with GCS of 13 or more were included in our study as only these patients undergo definitive surgery for ruptured aneurysm as per our institutional protocol. WFNS grade, which is commonly used to determine the prognosis following SAH, was also found to have a significant correlation with time to awakening following the surgery on univariate analysis. Since WFNS is based on GCS, it was not used in the generalized linear model to assess the impact on awakening.
In our study, the core body temperature at the end of surgery was found to be an independent predictor in determining the pattern of awakening in our study. The fall in temperature in our study was unintentional, and we found a significant correlation between patient's temperature at the end of surgery and the pattern of awakening following aneurysmal clipping for SAH was found. The observation of our study indicates that if the patients have a temperature below 35.3°C, then more than 80% of patients will have emergence that is delayed beyond 15 minutes. Over the past two decades, there has been a resurgence in the neuroprotective benefits of hypothermia after laboratory reports but the clinical evidence in humans is still lacking.,,, Todd et al. have reported that the use of mild intraoperative hypothermia (target temperature of 33°C) did not improve the neurological outcome in “good” grade patients undergoing aneurysmal clipping. Several other authors have not found any benefits of hypothermia over normothermia.,,,, The effect of intraoperative hypothermia on the long-term outcome was not evaluated as this was not the aim of the study, but delayed awakening can be assumed to be associated with the prolonged need for mechanical ventilation and hospital stay. The absence of robust evidence for neuroprotection with intraoperative hypothermia and the findings of our study would probably warrant caution against routine use of intraoperative hypothermia in patients undergoing intracranial aneurysm surgery.
A significant impact on time to emergence was seen with the Fisher grade in the generalized linear model in our study. A trend of increase in the time to awakening was seen with the rise in the Fisher grades. Although Fisher Scale was initially designed to predict cerebral vasospasm in patients with aneurysmal SAH, few studies have reported its correlation with clinical outcomes. The importance of conscious status in clinical grading and outcome need not be overemphasized. The initial Hunt and Hess grades and the initial Fisher grades have not been found to be reasonable factors for predicting the outcome of patients with ruptured intracranial aneurysms. However, the clinical importance of Fisher's radiological grading on time to emergence in our study needs to be emphasized. The patients with Fisher Grade 4 woke up at a median time of 3 hours when compared with 15 minutes in patients with lower Fisher grades. Higher SAH grades are more likely to be associated with cerebral vasospasm, raised ICP, disturbed autoregulation, cardiac arrhythmias and dysfunction, as well as water and sodium imbalance., This again is a reflection of the fact that the higher Fisher grades have a greater alteration of intracranial physiology and are consequently associated with longer awakening time.
TC of the parent artery decreases the blood flow inside the aneurysm thus enabling more precise dissection with decreased risk of rupture. Elective intermittent and shorter duration of TC have been associated with a favorable outcome. The use of TC has been found to have almost three times reduction in the risk of perioperative complications (intraoperative aneurysm rupture and inappropriate clip position). However, the risk of focal infarction secondary to induced flow arrest persists with the use of TC. Woertgen et al. observed that temporary vessel occlusion is an additional factor in aggravating vasospasm after aneurysmal subarachnoid hemorrhage. We observed a significant rank-order correlation with the duration of TC and time to emergence at the end of the surgery. This could possibly be due to the additional physiological insult related to the duration of ischemia to the affected part of the brain. In our study, as per institutional protocol, patients with TC were managed with a 20% to 30% increase in mean arterial pressure, and in case of prolonged clipping time, the patients were managed with an additional bolus dose of propofol.
Prolonged duration of surgery also bears a significant relation with delayed emergence. The duration of surgery more than 3 to 6 hours is associated with delayed emergence in patients undergoing supratentorial and infratentorial craniotomy., Our study observed a significant correlation of the duration of anesthesia with the time to awakening following neurosurgery. Longer duration anesthesia may influence the awakening following neurosurgery as there is a greater potential for pharmacophysiological impact on the acutely injured brain. The choice of the anesthetic agents, however, did not have any significant bearing on the time to awakening.
There are certain limitations of our study. First, the study is a prospective observational study done in only a modest number of patients. A large study would be needed in the future to support the present observations. Second, we did not record the comorbidities per se in the study and only considered the ASA physical status of the patients, since some comorbidities such as hypothyroid state can straightaway affect the emergence from anesthesia. Third, we did not collect data indicating reintubation in our study. Fourth, all the patients included in our study were operated by different neurosurgeons. The expertise of the different surgeons like the use of excessive retractor pressure and prolonged brain handling can impact awakening following neurosurgery. Moreover, the anesthesia protocol was not uniform. Although neurological outcome is an even better outcome parameter, there would have been multiple confounding factors, including the type of surgical procedure, possibly affecting our findings., Future studies need to assess how molecular alterations affect the outcome.
The present study has important observations with regard to the preoperative and intraoperative factors that can influence the awakening following anesthesia in patients undergoing neurosurgery following aneurysmal SAH. The preinduction GCS, patient's temperature at the end of surgery, Fisher radiological grade, duration of TC of the parent artery, and duration of anesthesia are independent predictors of awakening following surgery. The Fisher radiological grade and preinduction GCS are reflective of the impact of preoperative cerebral pathophysiology on awakening following surgery. The influence of duration of TC, duration of anesthesia, and patient temperature at end of surgery are suggestive of their secondary intraoperative effects on the brain and the consequent effect on the time to awakening following neurosurgery.
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Conflicts of interest
There are no conflicts of interest.
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