2. Chapter Two: Methodology
2.3. Methods
2.3.1. Sampling and the Participants
Study setting
This study was conducted at Aminu Kano Teaching Hospital (AKTH) located in Kano, the largest commercial city in Northern Nigeria. It was established in 1994, has a bed capacity of 600 beds and has Kano, Jigawa and Katsina States as main catchment areas. The hospital also receives significant number of patients from Bauchi, Yobe and Zamfara states as well as neighbouring Niger republic.
Study design
This study was a prospective, double blind, randomized controlled trial in which both the investigator and the parturient were blinded to the study drugs. All the parturients were randomized into two groups using opaque, sealed, numbered envelopes.
Group P: Parturients in this group received i.m pentazocine 30 mg in a 2 ml syringe.
Group T: Parturients in this group received i.m tramadol 100 mg in a 2 ml syringe.
Injection was only given after 3 cm cervical dilatation in the two groups.
Sample size estimation
A minimum sample size for this study was estimated using the formula below46;
[ Z
α√2π
1(1 - π
1) + Z
β√ π
1(1 - π
1) + π
2(1 - π
2) ]
2n = ---
(π
1- π
2)
2Where,
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n
= minimum sample size per groupZ
α= SD set at 95% = 1.96Z
β = power of the test to detect difference in analgesia between pentazocine and tramadol groups; set at 90% = 1.24π
1= proportion of parturients who had satisfactory analgesia with pentazocine from the previous study16 = 37% = 0.37π
2=proportion of parturients who had satisfactory analgesia with tramadol from previous study16 = 14% = 0.14So,
n
= [1.96* √ 2* 0.37* (1- 0.37) + 1.24* √ 0.37 (1- 0.37) + 0.14* (1- 0.14) ]2 (0.37 – 0.14)2n
= (1.3383 + 0.5987 + 0.1204)2 / (0.23)2n
= (2.0574)2 / (0.23)2n
= 4.2329 / 0.0529n
= 80.0170Therefore,
n
= 80 parturients / groupSo, the approximate sample size per group was 80 parturients.
This sample size was increased by its 10% to provide for attrition. Therefore, the sample size per group was 80 + 8 = 88.
This made the sample size in each group as 88 parturients.
Therefore, the approximate total sample size was 176 parturients.
Study population
xlviii Inclusion criteria
Booked parturients with Gestational age (GA) between 37 to 42 weeks
Request for analgesia
Spontaneous labour with cervical dilatation between 3 cm and 5 cm
Expectancy for uncomplicated vaginal delivery Exclusion criteria
Patient’s refusal to participate
Mute and psychiatric parturients
Known allergy to any of the drugs to be used
Labour with cervical dilatation more than 5 cm
Evidence of obstructed labour
Evidence of foetal distress
Presence of any obstetric/medical/surgical complications
Alcohol/drug abuse Consent
An informed consent form was made available to the parturients taking part in the study. The details of the procedure were explained to the parturients in the language they understood. Parturients were made to understand that their refusal would not in any way affect their management. Thereafter, an informed written consent was obtained either by signature or thumb printing as the case may be. (Appendix II)
Randomization Technique
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Parturients enrolled for the study were randomly allocated to one of the two groups.
One hundred and seventy six pieces of uniform sized sheets of paper were labeled P or T (88 each), representing the two study groups Pentazocine and Tramadol respectively. These papers were then folded and shuffled in a large box. For each parturient, an assistant took one folded sheet of paper from the box and the parturient is assigned to the treatment group indicated on the paper. The parturients hospital file number was then written on the sheet of paper. The paper was sealed in a separate envelope that was only opened after completion of the evaluation. Neither the interviewer nor the patient was notified of the group allocation.
Methodology
After the AKTH ethical committee approval was obtained to conduct the study (Appendix I); the departments of O & G and Paediatrics of the AKTH, Kano were duly informed before the study was conducted. The parturients received labour care according to the O & G departmental protocol. It involved assessing and recording of the non-invasive blood pressure, pulse rate and respiratory rate of the mother and foetal heart rate every 30 min. Other parameters like cervical dilatation, descent, presentation, rupture of membranes etc were all examined for and recorded at 1 h interval in the Partograph by the managing obstetricians. Parturients in spontaneous active labour with cervical dilatation between 3 cm and 5 cm at term with uncomplicated pregnancy were eligible for the study. Active labour was defined as regular uterine contraction at least three in ten minutes and cervical dilatation of at least 3 cm. However, the prospective parturients only enter into the trial on request for analgesia.
At the first request for analgesia the parturients were randomly allocated using the opaque, sealed, numbered paper into either Group P or Group T by the labour ward resident
l
(research assistant). The drugs were prepared in identical 2 ml syringes and administered by the attending midwife.
Group P: Parturients in this group were given i.m pentazocine (Ranbaxy laboratories Ltd., Dewas, India. NAFDAC # 04-0789) 30 mg in 2 ml syringe by the attending midwife.
Group T: Parturients in this group were given i.m tramadol (Mepha Ltd., Aesch-Basel, Switzerland. NAFDAC # 04-7266) 100 mg in 2 ml syringe by the attending midwife.
Parturients that requested for more analgesia within four hours of the initial dose were not given another dose; rather they were given psychotherapy by the researcher.
However, a repeat dose of either i.m tramadol 50 mg or i.m pentazocine 15 mg were given on request for more analgesia after at least four hours from the initial dose.
Unaware of the drug to be given, the researcher recorded the parameters at just prior to receive the i.m injection of the trial drug and at 30 min interval till delivery and immediately after delivery, 2 and 4 h after delivery, noting possible adverse effects and intervention using the Data collection form (Appendix III). Non-invasive blood pressure (systolic blood pressure, diastolic blood pressure & mean arterial blood pressure), pulse rate and respiratory rate of the mother (Smartsigns® Compact 750, Huntleigh Healthcare) and foetal heart rate (BD4000XS, Huntleigh Healthcare) were recorded at the said times.
The intensity of the labour pain as a measure of analgesic efficacy was assessed using a 10 cm marked VAS with 0 cm- representing no pain and 10 cm- representing worst pain imaginable. Maternal side effects; nausea, vomiting, sedation, pruritus and respiratory depression and the intervention given were looked for and recorded (see below for their management). The level of sedation when present was assessed using the Ramsay’s sedation score described as follows47;
li 1. Patient is anxious and agitated
2. Patient is cooperative, oriented and tranquil 3. Patient is drowsy but responds to command 4. Patient is asleep with brisk response to stimulus 5. Patient is asleep with a sluggish response to stimulus 6. Patient is asleep with no response to stimulus
Also, the time interval to the next request for analgesia and the duration of the labour were recorded.
Patient satisfaction was assessed on a Likert’s scale48 as follows;
Very poor – 1 Poor – 2 Good – 3 Very good – 4 Excellent - 5
The neonates assessment were done by the resident paediatrician on duty, who noted the Birth weight, APGAR scores at 1 & 5 min (and at 10 min if <7 at 5 min), and the need for special care baby unit (SCBU) admission were all noted as indices of foetal outcome. All the parturients were monitored for 4 h post delivery at 2 hr interval recording possible complications and interventions.
All the drugs used in this study were provided by the researcher. They included;
pentazocine, tramadol, naloxone and metoclopramide all licensed for use in Nigeria.
Protocol for the management of adverse effects;
Maternal:
lii Nausea/ Vomiting- i.v metoclopramide 10 mg stat
Respiratory depression (defined as respiratory rate <10 cycles per minute) - an incremental dose of i.v naloxone starting with 0.1mg plus Oxygen supplementation to fully reverse the depression
Neonatal:
Both assessment and resuscitation were done by the resident paediatrician on duty using suction apparatus, oxygen, i.v Naloxone (0.01mg/kg in incremental doses) and equipment for intubation among others.
Primary outcome measure was VAS scores at 60 minutes after drug administration.
While the secondary outcome measures were VAS scores at 30 minutes interval till delivery and after delivery, maternal side effects (nausea, vomiting, sedation, and respiratory depression), maternal cardiorespiratory (PR, SBP, DBP, MAP, RR) changes, FHR changes, neonates’ APGAR scores, admission into SCBU and maternal satisfaction.
Data analysis
Data obtained was analyzed using statistical package for social sciences (SPSS) version 15.0. Demographic variables were represented using tables and charts, percentages and graphs, while summary was done using means, standard deviation, frequency and percentages. Test of association for qualitative data was done using the Chi-squared test (or Fisher’s exact test where applicable), and for the quantitative data using the students t-test.
Level of statistical significance was set at p-value of <0.05.
liii