Clinical trial NCT03067740: Intraperitoneal Dexmedetomidine for Post-laparoscopic Appendicectomy Pain Management in Children
Official title: Intraperitoneal Dexmedetomidine as an Adjuvant to Bupivacaine for Management of Pain in Children Undergoing Laparoscopic Appendicectomy: A Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain, Postoperative
Keywords: appendicectomy
children
local anesthetics
laparoscopy
peritoneum
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2017-03-01
Enrollment: 56
Sex: ALL
Minimum age (years): 8
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fifty two children of American Society of Anesthesiologists (ASA) physical status I and II, aged 8-14 years old, of both gender, with suspected acute appendicitis scheduled for laparoscopic appendicectomy, were included in this study. Patients were randomized into group (B) and group (BD) with a 1:1 allocation ratio.At the end of surgery, and after peritoneal lavage, those patients who were allocated to B group (bupivacaine group; n = 26) received bupivacaine 0.25% intraperitoneally at a dose of 2 mg/kg followed by 5 ml normal saline. However, in group BD (bupivacaine, Dexmedetomidine group; n = 26), bupivacaine 0.25% at a dose of 2mg/kg was instilled intraperitoneally followed by dexmedetomidine 1mcg/kg diluted in 5 ml normal saline. In the postoperative period, assessments were made for pain and sedation on awakening in PACU (0 time) and at 2, 4, 6, 12,and 24 h. Abdominal and/or shoulder pain was assessed on the 10-cm Visual Analog Scale (VAS). Sedation was assessed using the Ramsay sedation score. Also the occurrence of nausea or vomiting was recorded . The time from extubation to the first administration of pethidine was registered. The consumption of postoperative analgesia was recorded. Side effects of the study drugs were assessed and recorded by the ward nurses for 24h postoperatively. Possible complications such as respiratory depression, allergic reactions, local anaesthetic toxicity,dizziness, , headache, were recorded and managed accordingly. Duration of surgery and length of stay in PACU were noted. Before discharge to home, length of stay in the hospital was recorded and parent's satisfaction was assessed using the 7-point Likert scale

Detailed description: A written informed consent for participation in the trial was obtained by parents or the legal guardians . Fifty two children participate in the study.

Randomization and blindness: Patients were randomized into group (B) and group (BD) with a 1:1 allocation ratio. The allocated intervention was written on a slip of paper, placed in a sealed serially numbered, opaque envelopes. The envelopes were serially opened, and the allocated intervention was implemented. Patients were equally distributed in both groups. All investigators, parents, and patients were blind to which method was being used.

Study description:

On arrival to the operating room, routine preoperative evaluation was performed, and the procedure was explained to all parents. Before premedication, patients and parents were instructed in the use of the 10-cm Visual Analog Scale (VAS),with score raging from 0 (no pain) to 10 (worst pain imaginable). Baseline measurements of heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and room air oxygen saturation (SaO2) were obtained using an electrocardiogram, a "Dinamap" automated blood pressure monitor, and a pulse oximeter, respectively.

All children received premedication with midazolam 0.05 mg/kg intravenously afterward, Ringer's lactate infusion (20 ml/kg/h) was started. Standardized prophylactic antiemetic was iv ondansetron 0.15 mg/kg. General anesthesia was inducted with propofol 2 mg/kg, rocuronium 0.6 mg/kg, and fentanyl 2 mcg/kg intravenously (i.v.). Endotracheal intubation was performed, tube size was calculated according to the formula: age/4+4. Anesthesia was maintained with a sevoflurane and oxygen mixture, with total fresh gas flow 3 L/min controlled by mechanical ventilation, tidal volume 5-10 ml/kg. The respiratory rate adjusted according to the end tidal CO2 (maintaining CO2 in the normal range of 35-45 mmHg). Standardized prophylactic antiemetic was ondansetron 0.15 mg/kg.

In both study groups, laparoscopic surgery was performed according to the standard surgical protocol. Local infiltration of port sites was performed by 4 ml xylocaine 1% at a maximum dose of 3 mg/kg. Standardized surgery involved 3 ports, a 5 or10-mm umbilical Hasson cannula and 3 or 5- mm left iliac fossa and suprapubic ports. Pneumoperitoneum was achieved using nonhumidified and nonheated CO2, with the intra-abdominal pressure maintained around 10-12 mmHg.

At the end of surgery, and after peritoneal lavage, those patients who were allocated to B group (bupivacaine group; n = 26) received bupivacaine 0.25% intraperitoneally at a dose of 2 mg/kg followed by 5 ml normal saline. However, in group BD (bupivacaine, Dexmedetomidine group; n = 26), bupivacaine 0.25% at a dose of 2mg/kg was instilled intraperitoneally followed by dexmedetomidine 1mcg/kg diluted in 5 ml normal saline. Surgeons instilled the study solution through a suction-irrigation device under visual control onto the parietal and visceral peritoneum of the right iliac fossa and pelvis to cover the appendix stump, lower pole of the cecum, and the terminal ileum. At the end of the operation, CO2 was cleared completely from the peritoneal cavity by manual compression of the abdomen with open trocar. Patients in both groups received intravenous paracetamol 15 mg/kg (Perfalgan, Bristol-Myers Squibb Pharmaceuticals Ltd, New York City, NY, USA).

Reversal of the muscle relaxant was carried out using prostigmine at a dose of 0.05-0.07 mg/kg and atropine at a dose of 0.02 mg/kg. The patients were then transferred to the postanaesthesia care unit (PACU) where monitoring of heart rate (HR), mean arterial blood pressure (MAP), respiratory rate (RR), arterial oxygen saturation (SaO2), and pain scoring was carried out. After operation, paracetamol 15mg/kg iv drip was administered on a regular base every 8h, and iv pethidine 1mg/kg as rescue analgesia ( whenVAS≥ 4) for the 1st 24. the occurrence of nausea or vomiting was recorded and patients were immediately given ondansetron 0.15 mg/kg if they experienced nausea and/or vomiting.

The ward nurses were instructed to omit the 6-h dose of pethidine if they considered that the patient was over sedated or pain free.

The time from extubation to the first administration of pethidine was registered. Side effects of the study drugs were assessed and recorded by the ward nurses for 24h postoperatively. Oxygen desaturation was considered when SpO2 dropped below 93% for more than 10 s. Bradycardia was defined as a HR 20% decrease from the baseline, whereas a HR more than 20% of the baseline was labeled as tachycardia. A drop in MAP by 20% or more of the baseline was regarded as hypotension while a MAP value higher than the baseline by 20% was regarded as hypertension. Other possible complications such as respiratory depression, allergic reactions, local anaesthetic toxicity,dizziness, , headache, were recorded and managed accordingly.

The primary outcome of the study:

In the postoperative period, assessments were made for pain on awakening in PACU (0 time) and at 2, 4, 6, 12,and 24 h. Abdominal and/or shoulder pain was assessed on the 10-cm Visual Analog Scale (VAS).

The secondary outcomes of the study:

* Sedation scores at PACU time and at 2h, 4h, 6h, 12h, and 24h after surgery.
* Time of first request of analgesia.
* Amount of rescue pethidine in 24h after surgery.
* Duration of surgery.
* Length of stay in PACU.
* Frequency of nausea and vomiting and other complications after surgery.
* Length of stay in hospital after surgery.
* Parents satisfaction before discharge to home.

Sample size calculation:

To calculate the sample size, the postoperative opioid consumption at day 1 in a similar clinical setting was taken into account. With a 2-tailed α = 0.05 and a power of 80%, we needed 23 patients in each group. Considering the anticipated drop out as 10%, 52 patients were asked to participate in the study. Data will be presented as a mean ± standard deviation, median, numbers, and frequencies, as appropriate. Statistical significance accepted at a P \< 0.05 Statistical analysis will be performed using SPSS program version 19 (Armonk, NY: IBM Corp.) and EP16 program. Student's t-test, Chi-square test, Mann-Whitney U-test, and Fisher's exact test will be used for statistical analysis, as appropriate.

Eligibility criteria: Inclusion Criteria:

* Patients are of American Society of Anesthesiologists (ASA) physical status I and II, aged 8-14 years old, of both gender, with suspected acute appendicitis scheduled for laparoscopic appendicectomy.

Exclusion Criteria:

* The diagnosis of developmental delay, attention deficit disorder, chronic pain, psychiatric illness, previous open abdominal surgery, the presence of a gastrostomy, ventricular-peritoneal shunt or other abdominal prosthesis, immunosuppression, and those allergic to any of the medications.

Primary outcomes:
measure: Postoperative abdominal and/or shoulder VAS pain score
timeFrame: at the start of postanesthesia care unit (PACU)(0 time), and 2 Hours, 4 Hours, 6 Hours, 12 Hours, and 24 Hours postoperative
Secondary outcomes:
measure: Time of first request of analgesia.
timeFrame: from the start of postanesthesia care unit (PACU time) and up to 8 hours
measure: amount of rescue pethidine consumed
timeFrame: in 24 Hours postoperative
measure: Length of hospital stay
timeFrame: from end of surgery till discharge to home, up to one week
measure: Sedation score
timeFrame: at the start of postanesthesia care unit (PACU)(0 time), and 2 Hours, 4 Hours, 6 Hours, 12 Hours, and 24 Hours postoperative
Other outcomes:
Locations:
city: Jeddah
country: Saudi Arabia
facility: Ali Elnabtity
Study officials:
References:
citation: Witt WP, Weiss AJ, Elixhauser A. Overview of Hospital Stays for Children in the United States, 2012. 2014 Dec. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #187. Available from http://www.ncbi.nlm.nih.gov/books/NBK274247/
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citation: Albanese AM, Albanese EF, Mino JH, Gomez E, Gomez M, Zandomeni M, Merlo AB. Peritoneal surface area: measurements of 40 structures covered by peritoneum: correlation between total peritoneal surface area and the surface calculated by formulas. Surg Radiol Anat. 2009 Jun;31(5):369-77. doi: 10.1007/s00276-008-0456-9. Epub 2009 Jan 14.
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