c Study with dental surgeons

Approval was obtained from the Research and Ethics Committee of the University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, and written informed consent was obtained from each patient before they were recruited into the study.

Research design:

This was a prospective, randomized double blind comparative study.

Study population:

The study population was American Society of Anesthesiologists (ASA) Physical Status Classification I or II, 40 – 90 year old male patients scheduled for elective TURP under spinal anaesthesia.

Study location:

This study was conducted in the University of Port Harcourt Teaching Hospital, Port Harcourt.

Determination of Sample size:

The sample size was calculated using the formula for comparison of mean:⁵⁵ n = (u+v)² x (SD1² + SD2²)

(µ1 - µ2)² n = sample size

u = one sided percentage point of the normal distribution corresponding to 100% minus the power (with power of 90%, u = 1.28)

v = percentage point of normal distribution corresponding to one sided

Significance level (with a significance level of 5%, 95% confidence interval, v = 1.96) SD1 = standard deviation of group 1 = 13mmHg

SD2 = standard deviation of group 2 = 16mmHg µ1 = mean of measurement of group 1 = 88mmHg µ2 = mean measurement of group 2 = 75mmHg

Using mean arterial pressures and standard deviations in the 2 groups of Ben-David et al study:⁵⁶ minidose bupivacaine-fentanyl spinal anaesthesia for surgical repair of hip fracture in the aged (bupivacaine with fentanyl = 88 ± 13mmHg, and bupivacaine = 75 ± 16mmHg) Therefore:

n = (1.28 + 1.96)² + (13² + 16²) (88 – 75)²

n = 4461.48 169 n = 26

Adding attrition rate of 10% = 26 + 3 = 29 per group.

Therefore 30 patients were recruited per group

Randomization:

Patients were divided into two groups according to letters (A and B) inserted into a sealed envelope; each group consisted of 30 patients. The study solutions A (isobaric bupivacaine 10mg with fentanyl 25µg (Duracaine Myungmoon, Kyungki-Do, Korea with Rotexmedica, Trittau, Germany) and B (isobaric bupivacaine 10mg (Duracaine Myungmoon, Kyungki-Do, Korea)) were prepared by another Anaesthetist (Research Assistant) who was not connected to the study. The investigator and patients were blinded to the study solutions; the study solutions were the basis of grouping of the patients, by the Research Assistant.

Inclusion criteria:

1. Patients scheduled for elective TURP.

2. ASA I or II patients between the ages of 40-90 years.

3. Patients who gave written informed consent for the surgery and the study.

Exclusion criteria:

1. Patients for emergency prostatectomy.

2. Patients that refused to participate.

3. ASA III, IV, or V patients.

4. Patients hypersensitive to amide local anaesthetic agents and fentanyl.

5. Patients with disorders of coagulation.

6. Those with infection at the lumbar region.

7. Patients in hyperdynamic state (hyperthyroidism).

8. Patients in hyponatremic state.

9. Spinal abnormalities and previous surgery on the spine.

10. Uncontrolled hypertension and diabetes mellitus.

11. Mental disturbance and neurologic diseases.

Technique of Anaesthesia

Preanaesthetic review of the patients was conducted the night before the surgery in their respective wards. This was to establish rapport with and clinically assess the patients, ascertain the effects and course of medical therapy. History also ascertained the possibility of coexisting morbid illnesses. Physical examination was done to check for pallor, dehydration, nutritional status of the patient; and the central nervous, cardiorespiratory, musculoskeletal and digestive

systems were examined to ascertain fitness for surgery and anaesthesia; the airway was assessed for feasibility of endotracheal intubation if the need arises.

Investigations were reviewed for proper patient selection (full blood count, electrolyte, urea and creatinine assay, electrocardiography, chest radiography), and additional tests when indicated from patient’s evaluation findings. The patients were classified using the American Society of Anesthesiologists Health status classification. The preanaesthetic plans included 6 hours and 2 hours preoperative fasting guideline for solid food and clear fluid respectively, grouping and cross-matching of 2 units of whole blood. The anaesthetic technique was explained to the patients and informed consent for anaesthesia was obtained. Preoperative anxiolysis was achieved overnight, with diazepam 5mg orally.

On the morning of the surgery, a pre-anaesthetic check was carried out on the anaesthetic machine, airway maintenance devices and suction machine; drugs in anticipation of possible conversion to general anaesthesia were made available. The study solutions (A and B) and resuscitation drugs were drawn up and labelled 30 minutes before the procedure.

Three carts were set up:

 Subarachnoid block cart containing the following: Solution A and B, 1% lidocaine, injection water, three 26G Whitacre spinal needles, syringes (2ml, 5ml, 10ml), hypodermic needles (21G and 23G), 0.9% sodium chloride infusions, sterile gauze, adhesive tape.

 General anaesthesia cart containing the following: propofol, suxamethonium, pancuronium, fentanyl, neostigmine, atropine, 2ml, 5ml, 10ml syringes, 21G and 23G hypodermic needles, 0.9% sodium chloride infusions.

 Resuscitation cart containing the following intravenous drugs: furosemide, epinephrine, atropine, ephedrine, 0.9% sodium chloride infusions, 2ml, 5ml, and 10ml syringes, 21 and 23 gauge hypodermic needles.

The patients were received in the operating theatre, identified using the patient’s tag and operation list, and transported to the urology theatre on a trolley.

Dash 4000 monitor manufactured by GE Medical system information technologies Inc. United State of America was used for monitoring. Arterial oxygen saturation probe, appropriate size non-invasive blood-pressure cuff, electrocardiographic (ECG) leads and axillary temperature probe were attached to the patient, and baseline vital signs like heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), arterial oxygen saturation (SaO2), electrocardiogram and axillary temperature were recorded.

Intravenous access was secured in the non-dominant upper limb with size 16G cannula.

Preloading was achieved by infusing 15ml/kg of warm normal saline infusion over 20 minutes.

Each patient were placed in the sitting position on the operation table by a trained assistant, with the feet supported on a stool such that the shoulders were in line with the axis of the surgical table. Under aseptic conditions, the lower back of the patients were cleaned with povidone-iodine, and draped. The L3 – L4 intervertebral space was identified, which corresponds with an imaginary line connecting the top of the iliac crests (Tuffier’s line). The underlying structures - skin, subcutaneous tissue, supraspinous ligament, interspinous ligament and ligamentum flavum were infiltrated with 3ml of 1% lidocaine using a 23G hypodermic needle.

The Subarachnoid space was located through the L3 – L4 intervertebral space using a 26G Whitacre pencil point spinal needle passed through an introducer needle (21G hypodermic needle). The needle was advanced through the midline and the underlying structures - skin, subcutaneous tissue, supraspinous ligament, interspinous ligament, ligamentum flavum, dural sheath into the subarachnoid space following a “give” on passing through the ligamentum flavum and piercing the dura sheath. An end point was reached as evidenced by the flow of cerebrospinal fluid following the removal of the stilet. All patients received 2.5ml volume of the study solution containing 2ml of isobaric bupivacaine (10mg) (Duracaine Myungmoon, Kyungki-Do, Korea). The study group (Group A) received fentanyl 25µg/0.5ml (Rotexmedica, Trittau, Germany) added to bupivacaine in the same syringe; the control group (Group B) received same volume of 0.9% saline added to bupivacaine. This was injected over 15 seconds with the needle aperture directed cranially, without barbotage or aspiration. Both the introducer and spinal needle were withdrawn and sterile dressing applied.

The patients were immediately returned to the supine position with a pillow support below the head and the shoulders. The blood pressures (SBP, DBP, MAP) were monitored and recorded;

baseline, every 3 minutes in the first 15 minutes, then every 5 minutes till the end of the surgery.

For the purpose of this study hypotension⁵⁴ was defined as systolic blood pressure ≤ 90mmHg or decrease of greater than 25% MAP from the baseline, and managed with intravenous fluid or and ephedrine 5mg. The HR, RR, SaO2, ECG, axillary temperature, and intraoperative blood loss were monitored continuously till the end of the surgery. For the purpose of this study bradycardia¹³ was defined as heart rate less than 50 beats per minute and was treated with intravenous atropine 0.6mg. Respiratory depression¹³ was defined as RR < 8 cycles/minute or SaO2 ≤ 85% in room air for the purpose of the study, and was managed with 100% O2 via a face mask at the rate of 4L/min. Normothermia was taken as temperature of 35.6 – 37.4ºC.

The level of sensory block was assessed using loss of temperature discrimination to a piece of cotton wool soaked in alcohol along the mid-clavicular line bilaterally extending to higher dermatomal levels, and the higher level was used for statistical purposes if the levels were not the same bilaterally.¹⁷ This was done every 2 minutes until the block reached an acceptable maximum (T10) and thereafter, every 10 minutes until there was two segments regression, and subsequently every 20 minutes till it regressed to S1. Motor block of lower limbs was monitored using the Bromage score⁵⁷ (0 = able to raise the leg and feet, 1 = able to flex the knee, 2 = unable to flex knees but with free movement of feet, 3 = no movement of the legs and feet). The quality of analgesia (pain score) was monitored using visual analogue scale⁵⁷ (VAS) (1 = no pain, 10 = worst possible pain) every 2 minutes till VAS ≤ 3 was obtained, and thereafter every 15 minutes till the end of surgery. Having achieved the desired level of pain score, sensory and motor blocks (VAS ≤ 3, T10 dermatomal level of sensory block and Bromage score 2), the patients were placed in the lithotomy position for surgery and diclofenac suppository 200mg was administered immediately per rectum for postoperative analgesia before the surgery commenced.

All patients received preoperative antibiotic prophylaxis (intravenous ceftriaxone 1g). The theatre temperature was maintained at 24ºC through out surgery, and intravenous and irrigant fluids were warmed before use. Bromage 2 and loss of cold or heat sensation at the dermatome

> L1 were considered adequate for transurethral resection of prostate.⁴⁹ The amount of glycine used and the duration of surgery were documented. Fluid maintenance was achieved intraoperatively with warm intravenous 0.9% saline solution at the rate of 4-8ml/kg/hr.

Intraoperative blood loss was estimated visually to be between 2.4 – 4.6 ml/min of resection

period and corrected with fluid 0.9% saline solution at the ratio of 1:3. Also the irrigation fluid bag height was kept at 60cm from the surgical field.⁶

At the end of surgery, the patients were transferred to the post-anaesthetic care unit (PACU).

All the patients were adequately covered with blankets to prevent the occurrence of shivering which may result from heat loss. In the PACU, the vital signs (SBP, DBP, MAP, HR, SaO2, ECG, axillary temperature, pain score, and sedation score) were monitored at the arrival of the patient (0 minute), then every 15minutes for 1 hour, hourly for 4 hours and thereafter 4 hourly for 24 hours.

The time from intrathecal injection of study agents to two dermatomes sensory block regression, regression of sensory block to S1 dermatome, and motor block regression to Bromage 0 were recorded. All durations were calculated in relation to the time of intrathecal injection. The duration of motor block was taken to be from the time of intrathecal injection of the study agent to the time of regression of motor block to Bromage 0. The duration of analgesia was taken as the time interval between the intrathecal injections of study agents to the time of first request for postoperative analgesia, which consisted of intravenous paracetamol 20mg/kg.

The postoperative doses of analgesics were recorded.

The patients having satisfied the criteria for discharge from the PACU like modified Aldrete⁵⁸ (see appendix III) score of at least 9, adequate respiration, not on oxygen, normothermic, regression of motor block to Bromage 0, VAS ≤ 3 were discharged to the ward for follow up;

pain score was monitored 4 hourly for 24 hours. Complications like pruritus, shivering, bradycardia, hypotension and respiratory depression were recorded and treated appropriately.

Data analysis

Data was analysed with SPSS 17 (Statistical Package for the Social Sciences, Chicago, IL) for windows. Tables and figures were used to present the result, and expressed as median (inter-quartile range), proportion (number of patients), and mean ± standard deviation. Chi-square test was used for test of significance between non-parametric variables – pre-existing pathologies, adverse effect incidences. Age, weight, height, surgery duration, baseline blood pressure, lowest blood pressure, and volume of glycine used were analysed with student’s t test. Mann–Whitney U test was used to evaluate the peak of sensory block level, maximum motor block score, and inter-group differences in the quantity of ephedrine used. A p-value of

< 0.05 was considered statistically significant.

Hypothesis

Null hypothesis (Hθ) - there is a difference in the spinal block characteristics between the combination of isobaric bupivacaine with fentanyl and isobaric bupivacaine alone.

Alternate hypothesis (Ha) – there is no difference in the spinal block characteristics between the combination of isobaric bupivacaine with fentanyl and isobaric bupivacaine alone.