Haemodynamic Consequences after Etomidate Administration for Short Surgical Procedures in Patients Aged Above 50 Years-A Prospective Study

1MD-Anaesthesiology, Government Medical College and Attached Hospitals, Kota, Rajasthan, India 2Senior Professor and Head of The Anaesthesiology Department, Government Medical College And Attached Hospitals, Kota, Rajasthan, India 3Assistant Professor in Anaesthesiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India Received date: 16 Sep 2017; Accepted date: 04 Oct 2017; Published date: 13 Oct 2017.


Introduction
Haemodynamic instability is one of the most common problems during general anaesthesia, many factors either solely or in combination, may be predisposing factors for it.Haemodynamic changes due to anaesthesia in various surgeries have become a great concern for physicians inside the operation room and evidence show that changes in blood pressure, either increase or decrease, independently are associated with side effects and complications in patients undergoing surgery [1].All methods used in anaesthesia induction are designed so that the haemodynamic stability is maintained especially in older patients [2].Intravenous anaesthetics are preferred for induction of general anaesthesia (GA) because of more rapid and smoother action with fewer risks.Cardiovascular and Respiratory systems appear to be minimally affected by Etomidate and myocardial oxygen supply-to-demand ratio is well maintained.Short operative procedures like closed reductions and plasters, abscess drainage, K-wire insertion, debridement of the wounds, K-wire removal, biopsy taking, VIU, wound dressing etc. require adequate depth of anaesthesia, muscle disorder and patients with presence of primary and secondary steroid deficiency.A detailed history regarding physical health, coexisting medical problems, current medications, allergies, previous anaesthetic and surgical experience were noted before surgery.Relevant laboratory investigations were reviewed.
The primary end point of this study was to determine the effects of Etomidate on heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure during anaesthesia induction, surgery and at 1 hour in post operative period in above mentioned group of patients and in enrolled patients with co-morbidities.
Secondary end points were evaluating the any complications regarding etomidate and required mean doses for completion of such surgeries.

Anaesthetic technique
On arrival of the patient in the operating room, after consent, fasting status and PAC checked, prior to induction anaesthesia machine, oxygen supply, suction resuscitation equipment and emergency drugs kept ready.After obtaining venous access with normal sized vein flow as per vein size an infusion of Ringer solution was started.The patient was connected to multi parameter monitor who records HR, non-invasive measurements of SBP, DBP, MAP, EtCO 2 , SpO 2 and continuous ECG monitoring.The baseline readings were recorded.After that, all patients were premedicated with injection Midazolam (0.25mg/kg), Glycopyrrolate (0.004mg/kg) and Fentanyl (2 mcg/kg) intravenously 10 minutes prior to procedure.Then patient was preoxygenated with 100% oxygen for 3 minutes via a face mask with Bain's circuit.Patient was induced with Etomidate 0.2 mg/kg loading dose.An additional dose of Etomidate 0.1 mg/kg was given intravenously if needed.Induction of anaesthesia was confirmed by loss of verbal communication with the patient and loss of eyelash reflex.Once an adequate depth of anaesthesia was achieved the patients were mask ventilated with 100% oxygen throughout operative time.Injection ondansetron 4 mg used to all for postoperative vomiting prophylaxis.

Recorded parameters
Haemodynamic parameters were recorded in all patients.Parameters were recorded at pre-operatively, 1 min, 2 min, 3 min, 4 min, 5 min, 10 min, 15 min and 20 minutes after induction.All parameters were also recorded post-operatively at 1 hour after completion of surgery.At the end of the operation, anaesthetic agents were discontinued allowing smooth recovery of consciousness.When the patient responded to verbal command to open the eyes, he was shifted to recovery room.

Statistical analysis
The data were analyzed using SPSS version 20 software for windows 7.All recorded data were expressed as mean ± S.D or mean (range) as appropriate.Paired t test was used for analysis of numerical data (HR, SBP, DBP, and MAP) in Intra-group comparison.The data of patients with comorbid conditions were also analyzed for changes in a heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure.P-value of less than 0.05 was taken to be statistically significant.

Observation and Results
In this study we enrolled 108 patients, in which 100 patients were included while eight patients were excluded from study because of nonmeeting of the inclusion criteria (patient refusal {n=1} and prolonged surgical time {n=7} who were managed with laryngeal mask airway; were the reason for these excluded patients).The results of 100 patients were observed and analyzed.

Demographic details of the participants (Table 1).
Mean age of patients was 63 years (62.94 ± 9.2691), while majority of the patients were male (62%) and belong to the age group of 51-60 years.Mean weight (kilograms) of patients was 64.64 kg ± 6.6447.In this study enrolled 83 patients were of ASA physical status-II; while 17 patients were of ASA physical status-III.
In this prospective study 46 patients presented with co-morbid illnesses i.e.Diabetes Mellitus, Hypertension, Chronic obstructive pulmonary disease, Ischemic heart disease and pulmonary tuberculosis etc. Majority of the patients were hypertensive (15 Hypertensive + 9 Diabetic-Hypertensive patients).We only enrolled patients undergoing short duration surgical procedures.The observed mean time in our study was 7.05 ± 1.707 minutes for completion of these surgical procedures.Majority of operative procedures were Visual internal urethrotomy (26%), swelling excision (22%) and closed joint reductions (17%).

Haemodynamic stability
The comprehensive and statistical analysis of changes in mean heart rate, mean SBP, mean DBP, and mean MAP values in response to administration of Etomidate at various time intervals were observed [Table 1, Figure 1(a,b,c,d)).
Baseline mean heart rate was 81.34 ± 11.29 beats per minute.Mean heart rate remained near to baseline values from the pre-operative time to till 1 hour of completion of surgical procedures.When the differences in changes of mean heart rate at various intervals were compared with baseline mean heart rate, it was found to be statistically insignificant (P>0.05).Baseline systolic blood pressure was 133.12 ± 12.86 mmHg.Mean SBP values remained near to baseline values from the pre-operative time to till 1 hour of completion of surgical procedures.When the differences in changes of mean systolic blood pressure at various intervals were compared with baseline Mean SBP, it was found to be statistically insignificant (P>0.(78.87 ± 7.14) from the pre-operative time to till 1 hour of completion of surgical procedures.When the differences in changes of mean diastolic blood pressure at various intervals were compared with baseline mean DBP, it was found to be statistically insignificant (P>0.05).Baseline MAP was 96.67 ± 8.37 mmHg.Mean MAP values remained near to baseline values from the pre-operative time to till 1 hour of completion of surgical procedures.When the differences in changes of mean MAP at various intervals were compared with baseline mean MAP, it was found to be statistically insignificant (P>0.05).We have not found any significant difference in SpO 2 at different time intervals in intra-operative period and post-operative period compared to baseline value.

05). Mean DBP values remained near to baseline values
As evident from the observation and result in our study, we observed and conservatively managed few of known complications.These were apnea (4%), myoclonus (18%), pain on injection (24%) and PONV (12%).

Discussion
Induction of anaesthesia is a critical part of anaesthesia practice, sudden hypotension, arrthymias, cardiovascular collapse are threatening complications, following administration of most of induction agents in haemodynamically unstable, old aged patients and even in haemodynamically stable patients.It is desirable to use a safe agent with least adverse effects of this purpose.An ideal intravenous anesthetic induction agent should provide a rapid but pleasant abolition of consciousness with minimal cardiovascular alterations, possess no side effects and have a short duration of action.Currently anaesthetic agents for induction are available in India as well as in United States are propofol, thiopentone sodium, ketamine and etomidate.Unfortunately, no one is ideal induction agents due to their own side effects.Myocardial and respiratory depression are very common with both propofol and sodium thiopental while ketamine has its specific bad emergence properties.[4][5][6].
Etomidate has minimal haemodynamic and ventilatory depression effects and does not trigger histamine release.Cardiovascular and Respiratory systems appear to be minimally affected and there is no indication of organ toxicity or other biochemical or haematological druginduced disturbance.[7,8].
Haemodynamic stability has been a hallmark of the induction of anesthesia with etomidate since this drug was introduced into clinical practice in the late 1970s.Etomidate produces minimal cardiovascular effects in healthy patients, as it maintains autonomic nervous system reflexes and preserves myocardial contractility [8][9][10] At typical anesthetic induction doses produces minimal blood pressure and heart rate changes in patients, including those with valvular or ischemic heart disease [8,9,[11][12][13].
Our findings of etomidate on mean heart rate corroborates with the comparative study of Mousumi Das, Basant ku Pradhan, Ramesh ch Samantray et al, 2015 [14 ].As from their study; In etomidate group, pre induction heart rate was 82.10 ± 5.24 bpm.In post induction heart rate was 80.76 ± 5.27 and after intubation 0 min, 1min, 3min, 5min and 10 min heart rate were 83.56 ± 5.06, 82.2 ± 4.91,82.73± 4.98,81.63± 4.8 and 82.33 ± 5.2 respectively.There were no significant changes in heart rate in post induction and after intubation as compared with pre induction.Also, there were no significant changes after intubation as compared with post induction.Our findings of etomidate on SBP corroborates with the comparative study of Mousumi Das, Basant ku Pradhan, Ramesh ch Samantray et al, 2015 [14].As from their study; In etomidate group pre induction SBP was 123.7 ± 5.54 mm Hg.In post induction SBP found 121.93 ± 5.43.Again, SBP after intubation 0 min, 1min, 3min, 5min, 10min were 124.03 ± 5.65, 123.93 ± 5.66, 123.43 ± 5.3, 122.56 ± 5.13, and 123.13 ± 5.7 respectively.There were no significant changes in SBP in post induction and after intubation compared to pre induction value and also no significant change after intubation compared to pre induction and post induction value.
Our findings of etomidate on DBP corroborates with the comparative study of Mousumi Das, Basant ku Pradhan, Ramesh ch Samantray et al, 2015 [14].As from their study; In etomidate group, pre induction DBP was 81.5 ± 4.82.In post induction, DBP was 79.16 ± 4.68 mm Hg.After intubation 0 min, 1min, 3min, 5min, 10min DBP were 81.36 ± 4.77, 81.32 ± 4.78, 81.3 ± 4.7, 79.9 ± 4.9 and 81.93 ± 5.0 respectively.There were no significant changes in DBP in post induction and after intubation compared to pre induction and after intubation compared to post induction.Our  Etomidate blocks adrenal steroidogenesis and hence cortisol synthesis, by its action on 11β-hydroxylase and cholesterol cleavage enzymes, and consequently decreases the hyperglycaemic response to surgery by approximately 1 mmol per litre in non-diabetic subjects [20].The effects of etomidate on diabetic patients have not been established.

Conclusion
Short recovery time, lack of hemodynamic instability at usual doses, relative low frequency of adverse drug reactions during the use of etomidate, provides optimal and safe conditions for short surgical procedures in critically ill, hemodynamic unstable patients and >50 years age group population with co-morbid illnesses.

Table 1 :
Changes in mean values of haemdynamic parameters from base line readings after administration of Etomidate for completion of short surgical procedures.