Análisis de Varianza con SPSS y R ESTADISTIC

METHODOLOGY

The study is a prospective, randomized, crossover study comparing 0.5mg/kg and 1.0 mg/kg suxamethonium as muscle relaxant in two successive treatment sessions of modified ECT carried out in same patients 48 hours apart.

Research Location

The study was carried out at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC) Ile-Ife. The hospital is a 580 bedded tertiary health institution established in 1975. It comprises of six units and serves a population of about 12 million people. The hospital has various medical and surgical specialties and subspecialties with the main facilities situated in Ife Central Local Government Area of Osun State, Nigeria.

Sample Size Determination

The sample size for the study was determined using sample size calculation for difference of means⁷⁹ which is given by

𝑛 = 2 𝑑²𝑥𝐶 Where n= sample size

d=Standardized difference = Target Difference Standard Deviation

Target Difference = Mean 1- Mean 2

C = Constant defined by p value and power (0.05 and 80% respectively)

Using a previous study²⁴, eye opening of recovery characteristics between unmodified group and propofol group showed;

Mean 1=7.40 minutes, Mean 2=5.80 minutes and standard deviation= 1.91

25 Therefore standardized difference, d = ^7.4−5.8_1.91 = 0.84

Therefore n = _0.84² ₂ x 7.9 = _0.7056² x 7.9 ≈ 22.392; 23 patients per group.

Allowing for attrition using a ratio of 10%, 3 patients were added. These were included in each group.

10% of 23=2.3; was approximated to 3.

Thus a sample size of 26 subjects per study group with a total of 52 ECT sessions was calculated. However, 27 subjects were recruited into the study giving a total of 54 ECT sessions.

Randomization Technique

All consenting patients that met the selection criteria were recruited by the Mental Health Physician for the study. They were randomized by the principal investigator to commence ECT course with either of the two doses of suxamethonium (0.5mg/Kg and 1mg/kg) being compared in the study using simple ballot. Each patient picked from an envelope containing equal numbers of shuffled papers coded A1 or B1 which signified 0.5mg/Kg and 1mg/Kg of suxamethonium respectively. Once picked the paper is not returned to the pool. Patients had the selected dose of suxamethonium; 0.5mg/Kg or 1mg/Kg in the first session of ECT. A patient who was administered with 0.5 mg/kg suxamethonium in the first session of ECT had 1.0 mg/kg at the second session and vice versa. Either of the two doses came first. The two consecutive sessions being compared were carried out 48 hours apart according to the standard ECT protocol. The patients, the assisting anaesthesia resident who prepared the drugs used, and the psychiatry senior registrar who administered the shock, and the principal researcher who observed and recorded the variables were all blinded to the grouping. The assisting psychiatry resident administered the drugs which he had drawn according to the study protocol and prepared in equal volumes. The role of each participant was defined and rehearsed before commencement of the study.

26 Ethical Considerations

Approval was obtained from the Ethical Committee of the OAUTHC. Informed written consent was obtained from the next of kin of all patients that satisfied the inclusion criteria.

Inclusion Criteria

1. Patients aged 18 to 65 years referred for modified ECT whose next of kin had given informed written consent.

2. Patients classified as American Society of Anesthesiologists’ Physical Status I or II Exclusion Criteria

1. Non-Consenting patient

2. Patients with features suggestive of pheochromocytoma.

3. Patients with anticipated difficulty with mask ventilation.

4. Individuals with liver dysfunction as determined by liver function tests 5. Major Burns in the last two years.

6. Patients with history of ischaemic heart disease.

7. Family history of malignant hyperthermia.

8. History of allergy to propofol or egg.⁸⁰

9. Anticipated difficult airway: Mallampatti III and above Conduct of Anaesthesia and ECT

All patients referred for modified electroconvulsive therapy by the Consultant Psychiatrist who satisfied the inclusion criteria and have given a written informed consent were recruited for the study. Informed written consent was obtained from the patients’

relatives after explanation on the need for, and the benefits of the procedure, possible

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challenges that might be encountered as well as likely adverse effects associated with ECT.

Satisfactory answers were given to relevant questions.

A detailed assessment was carried out before the commencement of a treatment course. All the patients were on hospital admission. Pre-anaesthetic review was conducted the day before administration of ECT. History of features suggestive of acute or chronic medical conditions was taken. History of drug therapy and or drug abuse was also taken and documented. Patients’ general conditions, level of consciousness and orientation as well as vital signs were assessed. Age, sex, American Society of Anesthesiologists (ASA) status, height, weight were documented. Airway assessment especially for the ease of mask ventilation was carried out by examining the jaws, mouth and the face for any abnormality.

Results of laboratory investigations including liver function tests (LFT), serum electrolytes, urea and creatinine and packed cell volume were also reviewed. An overnight fast was recommended. Regular sedative premedication was avoided.

ECT Procedure

Electroconvulsive therapy was performed before between 8:00 am and 12:00 noon in the procedure room equipped with anaesthesia machine (Boyle International^® 2 Serial Number: GCA 07, Medishield Harlow, England), a defibrillator; Cardioserv® (GE Medical Information Technologies Inc. Wisconsin, USA), a multiparameter patient monitor (Heal Force^® 120 Plus (2009) (Shenzhen Creative Co Ltd. China) and suction apparatus. Drugs and equipment for resuscitation (adrenaline, atropine, and sodium bicarbonate) were made available. Laryngoscope, appropriate sizes of endotracheal tubes, laryngeal mask airways, oropharyngeal airways and transparent face masks were made available.

Patients were encouraged to empty their bladder before the procedure as incontinence is common during seizures in ECT. The baseline heart rate (HR), systolic blood pressure

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(SBP), mean arterial pressure (MAP) and diastolic blood pressure (DBP) were taken and recorded before each treatment. This was repeated every three minutes during the procedure.

Arterial oxygen saturation (SpO2) and the electrocardiogram were monitored continuously.

Intravenous access was secured with size 18G cannula for drug and fluid administration.

Normal saline was used in all the treatment sessions.

Three millilitres of venous blood was withdrawn into Lithium Heparin bottle during venous cannulation for pre ECT serum potassium estimation. A second sample was similarly taken at the end of the induced motor seizures. The two samples were coded and kept in refrigerator at -4 degrees Celsius until they were sent to the Chemical Pathology laboratory for pre and post ECT serum potassium estimation immediately after the treatment session.

Patient was preoxygenated using a tight fitting face mask while breathing 100% O2 at 6 L/min for three minutes using a Bain circuit.

Propofol-Lipuro®, a preparation associated with minimal discomfort on intravenous injection was used in all the ECT treatment sessions⁸⁰. All patients had propofol 1mg/Kg for induction throughout the treatment course. Randomized dose of intravenous suxamethonium 0.5mg/Kg or 1mg/Kg was administered depending on which dose the patient picked from the envelope as earlier described, after isolation of the second upper limb not used for drug administration. The assistant, a registrar in anaesthesia, who was blinded to the dose of the suxamethonium observed maximal paralysis characterized by cessation of all fasciculation and absence of spontaneous breathing. During apnoea, oxygenation was maintained by administering 8 L/min oxygen through manual bag-mask ventilation till resumption of spontaneous respiration except during stimulus application. This was continued during the seizures. Bite block was inserted to protect the tongue immediately after suxamethonium induced fasciculation before administering the shock.

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Electrical shock was administered with Ectonus^® 5B, Serial Number 5CB 1012 (Ectron Ltd England) with maximum output of 700 millicoulombs and input of 80 Watts. A brief stimulus was delivered using ECT machine. The dose of ECT was determined by the attending Psychiatrist. Bi-temporal electrode placement was used for all patients. The same dose of ECT (150-200 millicoulombs) was used for all the treatment sessions evaluated in the study. The electroencephalogram is the preferred mode of monitoring seizures: However this was not readily available, therefore visible convulsion activity of muscles of the limbs and face was used as recommended by Whitehouse and Scott⁸¹. Seizure duration was taken from the moment the tonic phase of contraction was seen just after the shock was administered to the end of seizure using a stopwatch. Absence of visible involuntary motor activity on the limbs or face was considered as the end of seizure.

Quality of motor seizure was assessed on a five point scoring system⁵⁷ (Appendix B) using the isolated forearm technique with the aid of Accoson (England) manual sphygmomanometer cuff having blood pressure ranges of 0-300mmHg. The cuff was inflated to a pressure of 50mmHg above the systolic blood pressure to isolate the forearm before administration of suxamethonium. Quality of motor seizure was scored between one and five inclusive based on location and intensity of convulsions⁵⁷ as follows;

I- Violent convulsions similar to that seen in straight ECT.

II- Bilateral motor convulsions that is equal in intensity in both cuffed and un-cuffed limbs

III- Bilateral motor convulsions with the intensity more in cuffed limb when compared with corresponding un-cuffed limb.

IV- Motor convulsions are observed in cuffed limb and face.

V- Seizure is limited to the cuffed limb only.

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A score of V is the desired modification pattern in ECT. A score ≤ 2 indicates poor modification while 3 and above is considered acceptable.

Assessments

The major events during the procedure starting from administration of propofol, suxamethonium, loss of spontaneous respiratory efforts, ECT stimulus application, the end of physical convulsive activity and resumption of spontaneous breathing were all timed and recorded using a stopwatch by an anaesthesia resident who was blinded to the dose of suxamethonium used. Another assistant, a psychiatrist, blinded to the dose of suxamethonium recorded the duration of motor seizure. Both assistants assessed the extent of motor seizure using a five point as stated above. This was boldly printed, laminated and displayed in the ECT area.

The seizure modification pattern was defined as either poor or acceptable based on a 5-points modification score ³² (Appendix B). All patients with a score of one or two described respectively as violent convulsions like in unmodified ECT and bilateral motor convulsions that are equal in intensity in both cuffed and un-cuffed limbs had a poor modification. A score of three to five described as bilateral motor convulsions with intensity more in cuffed limb when compared with corresponding un-cuffed limb as a score of three, motor convulsions in cuffed limb as well as the face and motor convulsions only in cuffed limb as scores of four and five respectively, earned an acceptable modification. Pre and Post ECT Serum potassium was analysed and reported in the chemical pathology laboratory.

31 Post-ECT Care

The patient was placed in the left lateral position and oral suction performed.

Monitoring of vital signs was continued. Supplemental oxygen was continued via a transparent face mask until satisfactory level of recovery was attained and arterial oxygen saturation was adequate on room air. Discharge from recovery area was according to the modified Aldrete scoring system⁸². Patients were monitored in the ward thereafter by the attending nurses. Any side effects or complications especially headache, muscle pain, and nausea following procedure were reported. Patients with headache and muscle pain were reassured and treated with oral Paracetamol 10 mg/Kg.

Outcome Measures

The primary outcome measures of the study were:

1. Quality of seizure

2. Onset and duration of apnoea The secondary outcome measures were:

1. Changes in heart rate, systolic blood pressure, diastolic blood pressure, the mean arterial blood pressure and arterial oxygen saturation.

2. Side effects such as delayed recovery, muscle pain, vomiting, headache and prolonged seizures.

3. Pre and post ECT serum potassium.

Data Analysis

Data collected were entered into proforma and analysed using Statistical Package for Social Sciences (SPSS) version 17.0.

Parametric (continuous) data e.g. Height, weight, age, onset, duration of apnoea, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and serum

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potassium were all presented in means and standard deviations and compared using Paired t-test. Non-Parametric data such as seizure modification (acceptable or poor) and side effects were presented in frequencies and analysed with the chi-squared test or Fisher’s exact test as appropriate. Level of significance (p Value) was considered at 0.05.

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