Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05658406 |
| Other study ID # |
0305737 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 10, 2022 |
| Est. completion date |
September 27, 2022 |
Study information
| Verified date |
September 2022 |
| Source |
Alexandria University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Postoperative nausea and vomiting (PONV) is a common complication in the paediatric
population and is a source of significant morbidity. The incidence of PONV in children is
alarmingly high, as it is estimated to be between 33.2% to 82% depending on patient risk
factors. Even with the administration of prophylactic antiemetic medications, the risk of
PONV can still be approximately 30%. Various independent risk factors have been implicated in
the development of paediatric PONV. The following risk factors were identified: a duration of
surgery 30 minutes or longer, age 3 years or older, strabismus, adenoidectomy, and
tonsillectomy surgeries, a history of PONV in the child or immediate relatives (parents or
siblings), use of volatile anaesthetic, use of opioids, increased postoperative pain,
prolonged preoperative fast, and state of dehydration Significant improvement in patient
satisfaction can be achieved if the incidence of PONV is decreased. Although not usually
life-threatening, PONV may lead to complications commonly associated with vomiting, including
dehydration, electrolyte imbalance, and aspiration of gastric contents. In some surgical
cases, PONV has also led to wound complications, oesophageal rupture, subcutaneous emphysema,
pneumomediastinum, and bilateral pneumothorax. PONV typically describes nausea, vomiting, or
retching that can occur starting in the post-anaesthesia care unit (PACU) and continuing
through the 24 hours following surgery. PONV occurs twice as often in children than in adults
and can lead to longer PACU stays, delays in hospital discharge and subsequent unplanned
readmissions, which ultimately lead to significant financial burden on the patients.
A variety of antiemetic regimens are recommended for the prevention and treatment of PONV in
children, including pharmacotherapy with dexamethasone, 5HT-3 receptor antagonists,
butyrophenones, prokinetics, anticholinergics and antihistamines.
Hydration is yet another important factor in the development of PONV in paediatric patients.
Administration of intravenous dextrose-containing solutions may also prevent PONV.
Investigation of the effect of perioperative intravenous crystalloid administration on PONV
was initially motivated by the results of observational studies suggesting that perioperative
volume status influenced postoperative complication rates. This work showed that PONV was
among the most prevalent events after surgery and motivated subsequent inquiry into the
relationship between perioperative volume resuscitation and PONV .
Multiple reviews have explained the complex physiology of nausea and vomiting. Briefly, the
vomiting centre, located in the lateral reticular formation of the medulla, co-ordinates
efferent activity to the respiratory, gastrointestinal, and abdominal musculature to produce
vomiting. This centre receives afferent stimuli from a variety of sites: the pharynx,
gastrointestinal tract chemo- and stretch receptors, the brain (including vestibular
information from cranial nerve VIII), aortic baroreceptors, and the chemoreceptor trigger
zone. The chemoreceptor trigger zone is a neural centre physiologically outside of the
blood-brain barrier, which provides afferent information to the vomiting centre in response
to noxious stimuli in the blood.
Patients particularly paediatrics typically present for surgery with a fluid deficit
secondary to fasting, bleeding, bowel preparation, and other causes of dehydration. It has
been proposed that brainstem, vestibular, and intestinal hypoperfusion, with concomitant
ischaemia, may mediate nausea and vomiting. Supplemental intravenous crystalloids could serve
to mitigate this effect; however, no proven explanation for the putative role of volume
status in this model exists. Hypovolemia has been associated with a rise in postoperative
morbidity and mortality ranging from PONV to other complications such as organ dysfunction .
Hypovolemia from overnight fasting without adequate fluid replacement can cause adverse
effects postoperatively . Intravenous crystalloids are widely administered before, during,
and after procedures requiring general anaesthesia. They are inexpensive and have relatively
few adverse effects. A prior systematic review has suggested that supplemental intravenous
crystalloids may be effective in preventing PONV . However, studies of supplemental
perioperative intravenous crystalloids were noted to vary widely on the specific volumes
administered.
Despite evidence-based, multimodal prophylactic regimens, PONV remains a prevalent clinical
problem . The use of pharmacologic agents alone reduces the risk of PONV but increases the
risk of side effects. Intravenous crystalloids are an attractive treatment modality. Many
different intravenous fluid interventions have been tested in a wide variety of surgical and
anaesthetic contexts.
Description:
The aim of this study is to test the hypothesis that intraoperative supplemental intravenous
crystalloid fluid administration will reduce the incidence of postoperative nausea and
vomiting in paediatric patients undergoing oncological surgical procedures under general
anaesthesia.
Outcomes:
Primary outcomes:
We will analyse the risk of PONV occurring at different postoperative time points
postoperatively (i.e., early, late). The early postoperative period will be defined as the
period within six hours after surgery, while the late postoperative period will be defined as
the time nearest to 24 hours after surgery. PON was defined as an unpleasant sensation
associated with the urge to vomit. POV was defined as an attempted expulsion of gastric
contents (vomiting or retching). PONV was defined as any nausea, vomiting, or both.
Secondary outcomes:
1. Risk of requiring antiemetic rescue medication during the postoperative period.
Antiemetic rescue medication was defined as any additional intervention provided for the
treatment of established PON, POV, or PON.
2. Risk of suffering a serious adverse event (any of: admission to high-dependency unit,
postoperative cardiac or respiratory complication, or death).
3. To comprehensively determine the predictors of PONV as the dependant variable with age,
gender, weight, operative time, treatment group, pain, fever, and preoperative
chemotherapy as independent variables.
Patients and methods
This double-blind, prospective randomized controlled trial will be conducted in Borg Al-Arab
Children's Cancer Centre, Alexandria University Hospitals in Borg Al-Arab, Alexandria, Egypt.
After obtaining ethical committee approval and informed consent, we will study 100 patients,
aged 3-13 years, with a diagnosis of malignancy, undergoing surgery. Parents will be given
the option to give their children clear fluids up to 4 hours prior their arrival to the
operating room. Screened participants will be excluded if:
1. They personally had a history of PONV or motion sickness;
2. A sibling or parent or both, had a history of PONV.
3. They received antiemetic medication in the 24 hours preceding surgery.
4. Their BMI exceeded 30 kg/m2.
5. They had a history of cardiovascular or renal disease.
6. Developmental delay or mental retardation, or both.
7. They significant intraoperative blood loss (> 30% blood volume loss).
8. They had a history of cardiorespiratory disease.
9. They had a history of renal or hepatic diseases.
Patients will be prospectively and randomly assigned to one of the four groups (25 in each
group). Random sequence generation and allocation concealment will be done using
Computer-generated randomization. Supplemental crystalloid administration started after
induction of anaesthesia (intraoperatively), in addition to standard fluid management.
Patients will be divided into 4 groups:
1. Group A: intraoperative infusion of 15 mL/kg/hour Ringer's lactate.
2. Group B: intraoperative infusion of 10 mL/kg/hour Ringer's lactate.
3. Group C: intraoperative infusion of 6 mL/kg/hour Ringer's lactate.
4. Group D: standard fluid management alone.
Perioperative management:
All children will be given midazolam at 0.5 mg/kg orally for sedation 30 min in preoperative
holding area. Anaesthesia will induced with sevoflurane in oxygen. After induction a
peripheral IV cannula will be inserted for intravenous access; none of the patients will
receive any prophylactic antiemetic drugs. Anaesthesia will be maintained with endotracheal
tube (ETT), and controlled ventilation using atracurium, sevoflurane, and oxygen. Anaesthesia
will be supplemented with fentanyl 1 µg/kg during induction and a suitable regional analgesia
technique for surgery. Monitoring will include electrocardiogram, blood pressure, endtidal
CO2, temperature and pulse oximetry. The ETT Will be removed at the conclusion of surgery
under a deep plane of anaesthesia.
Postoperative care will be standardized. Rescue antiemetics will be administered to patients
if they were severely nauseated or vomited on more than one occasion using ondansetron 1-2 mg
i.v., analgesia will be given to children complaining of pain using a pain scale monitoring
for toddlers and young children. This will be consisted of oral analgesia (paracetamol).
Perioperatively, the study investigators and postanesthesia care unit (PACU) nurses will be
blinded to the allocation of the groups and the amount of fluid the subjects received.
