Postspinal hypotension in elderly patients undergoing orthopedic surgery, prophylactic ephedrine versus polygeline 3.5.

CONTEXT: Perioperative fluid management in elderly poses considerable challenge to the anesthesiologist. The conventional crystalloid loading may not be a preferred regime in this subgroup of patients since an exaggerated hemodynamic response is expected due to blunted sympathetic response and compromised cardiorespiratory system. AIMS: This study was designed in the elderly patient for comparing efficacy, side-effects and limitations of prophylactic ephedrine 30 mg (intramuscular [i.m.]) versus polygeline 3.5% 500 ml (intravenous [i.v.]) for the maintenance of blood pressure after subarachnoid block (SAB). SETTINGS AND
DESIGN: The sample size of 100 elderly (age > 50 years) patients undergoing orthopedic surgeries was administered SAB using bupivacaine 0.5% heavy. The primary outcome of this study was the attenuation of hypotension due to SAB using ephedrine or polygeline 3.5%.
MATERIALS AND METHODS: A total of 100 patients were randomly allocated to receive ephedrine 30 mg i.m. 10 min before the institution of SAB in Group I and preloading with 500 ml of polygeline 3.5% i.v. over 10 min prior to SAB in Group II. Patients in both groups were closely monitored for pulse rate, systolic blood pressure; any hypotension, requirement of rescue therapy and adverse effects. STATISTICAL ANALYSIS USED: Results were interpreted using Student's t-test for parametric and Chi-square tests for nonparametric data.
RESULTS: The incidence of hypotension and requirement for rescue therapy was statistically less in Group I compared with Group II (P < 0.05). Heart rates were better maintained in Group I than Group II, with few hemodynamic adverse effects in both groups.
CONCLUSIONS: Ephedrine 30 mg i.m. given as pretreatment before SAB in elderly patients was more effective for the prevention of post-SAB hypotension.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Geriatrics, constituting approximately one fourth of surgical population, requires special perioperative care as these patients suffer from chronic ailments despite great advances in medicine. Regional anesthesia, most commonly subarachnoid block (SAB) is preferred in elderly patients to avoid the various complications and the postoperative disruption of mental functioning with general anesthesia.[1] However, the associated hypotension has a reported incidence of 25-80% in the elderly.[2]

The maintenance of perioperative hemodynamics during spinal anesthesia has been attracting the attention of researchers since decades; with crystalloid loading being the most favored regime. However, this regime may be unsuitable for the elderly population for the fear of fluid overload. Various colloid solutions have also been added to crystalloids by various researchers, but their effectivity and safety may not cover the in elderly population.[3] This is due to progressive and universal attrition of complex integrated autonomic reflexes responsible for failure of cardiovascular homeostasis in aged population.

Among the vasopressors, ephedrine has been a commonly used agent for managing spinal hypotension since 1927. However, its use in elderly has not attained clear consensus due to fear of tachycardia and hypertension associated with its use.[24]

The purpose of our study was to compare the efficacy of the two alternative regimens as prophylaxis for the prevention of SAB induced hypotension. Injection ephedrine 30 mg and colloid preloading was achieved with polygeline 3.5% for this purpose.

MATERIALS AND METHODS

This study was conducted on 100 patients of age more than 50 years and weight between 55 and 65 kg undergoing orthopedic surgeries on lower limb under SAB after approval from institutional review board. The patients were comparable with respect to age, height, type of anesthesia, cardiac risk index, and preoperative parameters. They were allocated randomly to either of the regime groups after written informed consent and due approval from the Hospital Ethics Committee [Figure 1].

Figure 1

Consort diagram showing the selection and randomization of patients

All patients were assessed clinically and only American Society of Anesthesiologists (ASA), I, II and III selected for the study. Patients with severe respiratory or cardiac disease (cardiac arrhythmias, abnormal cardiac anatomy or congestive cardiac failure), on medications such as digoxin or β-blockers that could alter the normal response to our treatment, uncontrolled hypertension, significant dehydration, any contraindication to SAB and a hemoglobin <10 g% were excluded.

Patients were classified as hypertensive if they had a baseline SAP of >150 mmHg or if they were receiving regular treatment for it. The antihypertensive medications were taken note of and continued preoperatively.

Routine investigations such as hemoglobin, blood sugar, blood urea, Rh typing, coagulation profile, X-ray chest and electrocardiogram (ECG) were carried out. Additional investigations were conducted as per individual requirements. As per institutional policy, all the patients received tab diazepam 5 mg on the night before the surgery to allay anxiety and fasted overnight.

On arrival to the operating room, an 18-gauge intravenous (i.v.) cannula was inserted and routine cardiovascular monitoring equipment attached to record baseline parameters like noninvasive arterial blood pressure, heart rate (HR), ECG and pulse oximetry (SpO2).

In Group I, injection ephedrine 30 mg (intramuscular [i.m.]) was administered 10 min before induction of SAB. Patients were observed for any changes in cardiovascular parameters.

In Group II, injection polygeline 3.5% 500 ml (i.v.) was infused over 10 min just prior to SAB with constant vigilance for any signs of allergic reactions or fluid overload in addition to the hemodynamic monitoring.

Spinal anesthesia was instituted in all cases in the lateral position, at L2-3 or L-4 level, using 0.5% hyperbaric bupivacaine, volume depending on patients’ weight, height, sex and physical condition.

Sensory level was confirmed at 5 and 15 min. intervals with pinprick. Maintenance infusion of injection Ringer's lactate was administered to both the groups as calculated according to the conventional 4-2-1 rule.[4] Redistribution and evaporative surgical fluid losses were replaced with 4 ml/kg of crystalloid.[4] Blood was transfused if the losses summed up to 10-20% of the blood volume.

Systolic blood pressure (SBP) and diastolic blood pressure were measured at 2-3 min intervals until 10 min. after induction and at 5 min. intervals thereafter. An episode of hypotension was defined as a fall in SBP by 25% of the baseline (mean of three consecutive readings) or an absolute value <90 mm of Hg; treatment was instituted only if the next reading taken 1 min apart also showed persistent hypotension. Any SBP variation of 25% from the baseline or an absolute value of 90 mm of Hg was observed carefully.

Episodes of hypotension were treated with i.v. boluses of injection Ringer's lactate 2.5 ml/kg. A maximum of three boluses were given, and if SBP remained <75% of baseline, injection ephedrine (6 mg) i.v. was also given.

Postoperatively, the patients were followed-up for any complications or hemodynamic instability.

Statistical analysis

The data were compiled and statistically analyzed using “Chi-square” and “Student's t-test.” The previous studies have selected 45-60 patients to evaluate hypotension after SAB using various regimes. For our study, we included larger number of patients to decrease the β error. Taking an α error of 0.05, post-hoc analysis to compare the episodes of hypotension for the sample size of 100 revealed that power of the study (1−β) to be >90%.

OBSERVATIONS AND RESULTS

The demographic data and the vitals were statistically comparable in both groups [Table 1]. Majority of the surgeries were of 1 to 2 h duration.

Table 1

Demographics and vital data

The sensory level, number of episodes of hypotension, hemodynamic effects, and amount of fluid required were compared using Chi-square analysis.

After sub arachnoid block, 46% of patients of Group I (ephedrine) and 66% of Group II (polygeline 3.5%) attained T6 level and 52% of Group I and 30% of Group II got T8 level; these values are statistically comparable (P > 0.05).

Figure 2 shows higher perioperative pulse rates in Group I compared to Group II, with the difference being statistically significant (P < 0.05) from first 4 min to 30 min after SAB; however these readings are within acceptable levels.

Figure 2

Mean pulse at different time intervals during the 1st h P < 0.05; significant at 4 min, 5 min, 10 min, 20 min, 30 min

The perioperative SBP at different time intervals [Figure 3], indicates a maximum fall occurred up to 10 min following SAB in Group I and at 20 min in Group II; there was better hemodynamic stability in Group I.

Figure 3

Mean systolic blood pressure at different time intervals during the 1st h

Table 2 shows the number of patients who developed hypotension, intra-operatively at any given time (<75% of preoperative SBP). By applying Chi-square test, episodes of hypotension are seen to be statistically higher in Group II than in Group I with P < 0.05.

Table 2

Number of patients who developed hypotension intraoperatively (<75% of preoperative SBP)

All the patients of Group I received only single bolus of fluid whereas majority of patients of Group II required three boluses of fluid along with injection ephedrine to maintain the blood pressure. The total number of rescue doses given to the patients who developed hypotension in Group I is statistically less as compared to Group II [Table 3].

Table 3

Rescue therapy in patients who developed hypotension

No serious adverse effects were observed [Table 4]. Tachycardia was observed in some patients of Group I (three patients) although incidence of bradycardia was more in Group II (five patients) than in Group I (one patient). Hypertension was observed in two cases of Group I.

Table 4

Complications (hypotension elaborated in Table 2)

The postoperative course of the patients was uneventful with mean pulse rate in Group I being 86.68 and in Group II 87.72; mean SBP in Group I being 118.64 and 110.82 in Group II.

DISCUSSION

Orthopedic interventions posing need for perioperative anesthetic management have become even more commonplace in elderly, with increased number of patients presenting for joint replacements and fracture fixation. SAB provides superb operating conditions with a drier surgical field, reduced blood loss, lower incidence of deep vein thrombosis and pulmonary embolism, postoperative analgesia and above all the maintenance of mental function.[1] Reduced physiological reserve and chronic diseases predispose them to long term complications after hypotension particularly coronary artery disease and cognitive behavioral dysfunction.[35]

Management modalities for hypotension include volume resuscitation and vasopressor therapy. The efficacy of crystalloid loading, which dates back to 30 years, is still under doubt. Over and above, these benefits seem doubtful in elderly population who have higher propensity to develop hypotension because of reduced sympathetic tone. Moreover, poor cardiac reserve giving rise to significant increase in central venous pressure, pulmonary edema and hemodilution, simultaneously increasing the need for urinary catheterization.[1]

Ephedrine has been the first agent to be used successfully to treat hypotension induced by SAB in 1927. It is sympathomimetic with both α-, β-adrenergic activity and also releases noradrenaline from storage sites. There are numerous studies that have proved its role in preventing hypotension after SAB targeting obstetrics and orthopedic surgeries.[467] We chose elderly population for our study to evaluate its effectiveness as a vasopressor for maintaining hemodynamics without crystalloid loading. i.m. route has been preferred for the fear of tachyphylaxis with repeated i.v. injections.

Our study shows higher pulse rates with ephedrine in the first half hour after administration of spinal anesthesia, which may also have contributed to better hemodynamic stability by maintaining the cardiac output. It is feared that it may be ineffective in reversing the spinal induced decrease in systemic vascular resistance, possible because of its β-agonist effect causing arteriolar dilatation in opposing to α vasoconstrictor effect. Moreover, its β mediated increase in HR may expose elderly patients with latent coronary disease to myocardial ischemia.[8] However, in our study, elderly patients of ASA Group, II and III maintained hemodynamic stability in ephedrine group, albeit tachycardia in few cases.

Colloid solution is proposed to be more effective for its large molecular weight ensures longer intravascular retention and avoids overcorrection of hemodynamics seen with vasopressors.[8910] A plausible explanation for the failure of injection polygeline in the elderly may be that the reduced physiological reserve in the elderly patients make them less able to respond to volume by increasing cardiac output.

This study also emphasizes the role of i.v. fluids in maintaining preload and thus cardiac output as the patients of Group I were well hydrated, whereas those of Group II received 500 ml of fluid in the form of colloid in addition to their maintenance fluid requirement.

Our results are in accordance with other studies on the management of hypotension occurring during central neural block where crystalloids, colloids and vasopressors have been used alone or in combinations.[3810] McCrae and Wildsmith concluded that each patient should be treated on individual merit, recognizing that many factors may influence arterial pressure during anesthesia and surgery.[11] Similarly Morgan also concluded in his study on regional anesthesia induced hypotension that there is no single management strategy.[12] The meticulously calculated administration of crystalloids in our study worked well in conjunction with prophylatic vasopressor, whereas, with colloid preloading incremental fluid boluses were administered.

The complications of ephedrine as documented in literature include central nervous system symptoms: Vertigo, headache, vomiting.[12] These symptoms were not observed in our study, which may be due to difference in dose and route of administration.

CONCLUSION

This prospective, randomized, singe blinded, clinical study involving a comparison of two different measures intended to reduce hypotension post-SAB in elderly patients showed greater hemodynamic stability with preemptive injection ephedrine, 30 mg (i.m.), given 10 min before sub arachnoid block compared with an infusion of injection polygeline 3.5% 500 ml.