Clinical trial NCT03846284: Caudal Versus Intravenous Magnesium Sulfate on Emergence Agitation After Sevoflurane In Children.
Official title: Caudal Versus Intravenous Magnesium Sulfate In The Prevention OF Emergence Agitation After Sevoflurane Anesthesia For Lower Abdominal Surgeries In Children.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Emergence Agitation
Postoperative Pain
Keywords: Sevoflurane-
Emergence agitation
Magnesium sulfate
Children
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2019-02-19
Enrollment: 93
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: , prospective, blind,controlled clinical trial
Primary purpose: PREVENTION

Brief summary: Sevoflurane is the agent of choice for induction and maintenance of day care anesthesia in children and has a wide acceptance among pediatric anesthesiologists.

Emergence agitation (EA) is a frequent postoperative complication in pediatric patients receiving inhalational anesthetics with a rapid recovery, e.g. sevoflurane Magnesium sulfate is a non anesthetic N-methyl-D-aspartate receptor antagonist, Regional anesthetic techniques have major two benefits which are lowering anesthetic requirements intraoperatively and providing adequate postoperative pain relief.

Magnesium sulfate is an adjuvant that alters the perception and duration of pain by serving as an antagonist of N-methyl-D-aspartate glutamate receptors. Caudal injection of bupivacaine with magnesium sulfate in pediatric patients after inguinoscrotal operations provided adequate postoperative analgesia without producing many side effects. Caudal block with local anesthetic with or without adjuvants may prevent emergence agitation with effective postoperative pain management.

* So the aim of this study is to compare the efficacy of caudal versus intravenous magnesium sulfate infusions in controlling emergence agitations after inhalational sevoflurane anesthesia in children who will undergo lower abdominal surgeries.

Participants and methods

All participants will receive caudal block with bupivacaine 0.25% 1mg/kg dialed in 10 cm saline.

The participants will be divided to 3 groups

1. Bupivacaine group (B group) (group 1) N = 31 :-
2. Magnesium sulfate caudal group (MC group) (group 2) N = 31 :-
3. Magnesium sulfate I.V group (MV group) (group 3) N = 31 :-

Postoperative assessment in the ( PACU):-

* The oxygen saturation (SO2), heart rate (HR), and mean arterial pressure (MAP) are monitored by the observer blinded to group allocation on admission and 10 mins till discharge (0, 10, 20, 30, 40, 50, 60mints, time of discharge) from the PACU.
* Emergence agitations (Pediatric anesthesia emergency delirium scale (PAED) The presence of Emergence agitation and its severity will be measured using (PAED).

The presence of Pain and its severity will be measured using FLACC scale.

* Time of first postoperative administration of fentanyl in mints
* Modified Aldrete score :- The discharge from the PACU will be measured using Modified Aldrete score.

Detailed description: Participants and methods All participants will receive caudal block with bupivacaine 0.25% 1mg/kg diluted in 10 cm saline.

The participants will be divided to 3 groups

1. Bupivacaine group (B group) (group 1) N = 31 :- The participants will receive caudal block with bupivacaine 0.25% 1mg/kg diluted in 10 cm saline.

   + I.V injection of 10 cm saline over 10 mins then, followed by I.V infusion 50 cm saline with rate 10-20 ml/h according to child weight.
2. Magnesium sulfate caudal group (MC group) (group 2) N = 31 :- The participants will receive caudal block with bupivacaine 0.25% 1mg/kg plus Magnesium sulfate 50 mg diluted in 10 cm saline.

   * I.V injection of 10 cm saline over 10 mins then, followed by I.V infusion of 50 cm saline with rate 10-20 ml/h according to child weight.
3. Magnesium sulfate I.V group (MV group) (group 3) N = 31 :- The participants will receive caudal block with bupivacaine 0.25% 1mg/kg diluted in 10 cm saline.

   + I.V injection of Magnesium sulfate 30mg/kg diluted in 10 cm saline over 10 mins then, followed by I.V infusion one ampule of Magnesium sulfate 500mg diluted in 50 cm saline with rate 10 mg/kg/h.

   Standard monitoring is used during anesthesia and surgery include :- electrocardiography, non-invasive arterial pressure, arterial oxygen saturation using pulse oximeter and end-tidal concentrations are measured using capnography.

   An intravenous line is secured before induction of anesthesia, all participants will receive a standardized rapid sequence induction of anesthesia and oxygen administration for 3 minutes. Anesthesia is induced with Inhalation of 8% sevoflurane without use of muscle relaxant, cricoid pressure is applied and the trachea intubated with a suitable-size endotracheal tube. Maintained end-tidal sevoflurane concentration will be between 2.5-3.5 and will be titrated. The participants will breath spontaneously during surgery and tidal volume will be adjusted to maintain normocarbia. I.V injection of 0.2 mg/kg dexamethasone after induction as a prophylaxis of post-operative nausea and vomiting of Mg sulfate. Caudal block will be performed to participants before surgical incision with 1 of 2 investigators using the following technique :- The Participants are placed in left lateral position after induction of general anesthesia. The back of the participant including the sacral hiatus are carefully sterilized with an antiseptic solution and sterile drapes will be placed around the injection site. The technique will be done by introducing a 23-gauge hypodermic needle perpendicular to the sacrococcygeal membrane with the bevel in the direction of the long fibers of the membrane. The needle will be inserted until there is release of impedance as it pierced the sacrococcygeal membrane. Then, it is directed upwards so that it make an angle of 20-30° with the skin about 2 mm so that the whole bevel will be inside the sacral canal. The injection will be made over a period of about 60 s and then a small elastoplast dressing is placed over the injection site and the participant will be placed supine. Intraoperative analgesic supplement will not be given.

   Caudal block will be failed if HR \&/or MAP increased 10 more than the previous basal value of beginning of surgery.participants will be fasting 4-6 hours for solid foods and 2 hours for clear fluids. Balanced fluid therapy containing Na Cl, glucose, K and Ca will be infused according to body weight as follows :1st 10 kg 4 ml/kg/hour, 2nd 10 kg 2 ml/kg/hour and 1 ml//hour for every 1 kg.

   Then, anesthetic gas discontinued and replaced O2 100%. At the end of the operation the trachea is extubated, The participants will be transferred to the postanesthesia care unit (PACU).

   Intraoperative assessment:-

   • Heart rate (HR) and mean arterial blood pressure (MAP), oxygen saturation (SO2) are recorded basal before operation and every 10 mins. until the end of surgery.

   • minimal alveolar concentration (MAC) of sevoflurane is recorded every 10 mins.

   • The occurrence of intraoperative hypotension (defined as systolic arterial pressure 70 plus twice the age in years and associated with altered peripheral perfusion), requiring a fluid bolus.
   * The occurrence of intraoperative bradycardia (defined as heart rate below 60 beats min for ages above 1 years), requiring atropine.
   * Duration of anesthesia: it is the time from start of inhalation induction by sevoflurane till tracheal extubation in mins.
   * Extubation time: it is the time from termination of sevoflurane to tracheal extubation in mins.
   * Emergence time: it is the time from the end of surgery till the opening of patient's eyes in mins.
   * Interaction time: it is interval between stopping sevoflurane and verbal or physical response in mins. All are noted.

   Postoperative assessment in the ( PACU):-
   * The oxygen saturation (SO2), heart rate (HR), and mean arterial pressure (MAP) are monitored by the observer blinded to group allocation on admission and 10 mins till discharge (0, 10, 20, 30, 40, 50, 60mints, time of discharge) from the PACU.
   * Emergence agitations (Pediatric anesthesia emergency delirium scale (PAED):- The presence of Emergence agitation and its severity will be measured using (PAED).

   Item 1. The participant makes eye contact with care giver 2. The child's actions are purposeful 3. The child is aware of his/her surroundings 4. The child is restless 5. The child is inconsolable - Items 1, 2 and 3 are scored: 4 = not at all, 3 = just a little, 2 quite a bit, 1 = very much, 0 = extremely.

   - Items 4 and 5 are scored: 0 = not at all, 1 = just a little, 2 = quite a bit, 3 = very much, 4 = extremely.

   It will be monitored on admission and every 10 mins till discharge from the PACU (0, 10, 20, 30, 40, 50, 60 mins, time of discharge).

   PAED score ≥ 10 will be managed by intravenous doses of fentanyl 1micg/kg, repeated after 10 min if the child is still agitated, with a maximum total dose of 2 micg/kg. (PAED) score ≥ 10 will be considered to be a diagnostic endpoint for the development of agitation.

   • Pain score (FLACC scale) :-

   The presence of Pain and its severity will be measured using FLACC scale.

   CATEGORIES SCORING

0 1 2 Face

No particular expression or smile Occasional grimace or frown, withdrawn, disinterested. Frequent to constant quivering chin, clenched jaw. Legs

Normal position or relaxed. Uneasy, restless, tense. Kicking, or legs drawn up.

ACTIVITY

Lying quietly, normal position moves easily Squirming, shifting back and forth, tense. Arched, rigid or jerking. Cry

No cry, (awake or asleep) Moans or whimpers;occasional complaint crying steadily, screams or sobs, CONSOLABILITY

Content, relaxed. Reassured by occasional touching hugging or being talked to, distractable. Difficulty to console or comfort

It will be monitored on admission and every 10 mins till discharge from the PACU (0, 10, 20, 30, 40, 50, 60 mins, time of discharge). If the FLACC pain scale score is noted at any time to be 4 or more, the patient will be given1micg/kg fentanyl I.V and repeated after 10 mins, if the participant is still in pain with a maximum total dose 2 mg/kg

* Time of first postoperative administration of fentanyl :- in mints
* Modified Aldrete score :- The discharge from the PACU will be measured using Modified Aldrete score. Items are :-

Activity:

2. able to move 4 extremities voluntarily or on command

1. able to move 2 extremities voluntarily or on command 0. unable to move extremities voluntarily or on command

Respiration:

2. able to breath deeply and cough freely

1. dyspnea or limited breathing 0. apneic

Circulation:

2. BP +/- 20% of pre-anesthetic level

1. BP +/- 20% to 49% of pre-anesthetic level 0. BP +/- 50% of pre-anesthetic level

Consciousness:

2. fully awake

1. arousable on calling 0. not responding

O2 saturation :

2. able to maintain O2 saturation \<92% on room air

1. needs O2 inhalation to maintain O2 saturation \<90% 0. O2 saturation \>90% even with O2 supplement. It will be monitored on admission and every 10 mins till discharge from the PACU (0, 10, 20, 30, 40, 50, 60 mins, time of discharge). Participants will be discharged from the PACU after adequate control of agitation and pain, and when they has achieved Modified Aldrete score characteristics of ≥ 9,

Postoperative complications :- All post operative complications are also recorded by the observer blinded to group allocation which include :-

* The occurrence of Postoperative nausea and vomiting (PONV) :-
* (PONV) is treated as needed with i.v.ondansetron 0.06 mg/kg every 4 h.
* The occurrence of postoperative respiratory depression (defined as oxygen saturation below than 95%) and respiratory rate below than 10 breaths/min.
* The occurrence of Postoperative Laryngospasm or Bronchospasm.
* The occurrence of postoperative Hypotension definition and treatment as mentioned before.
* The occurrence of postoperative Bradycardia definition and treatment as mentioned before.

Statistical analysis

Statistical analysis will be done by using statistical package for social scientists (SPSS) program version 16. Data will be proved parametric by using kolmogorov -Smi mov test. The quantitative data will be presented in the form of mean and standard Deviation. One-way ANOVA test will be used to compare between quantitative data of the three groups. Paired t-test will be used to study between two values in the same group. Pain score, sedation score will be represented by median and range and will be analyzed by Kruskal-Wallis test to compare between the three groups. Mann-Whitney test will be used for comparison between 2 groups separately. Significance will be considered when P-value is less than 0.05

Sample size The primary outcomes was the incidence of emergence agitation. A previous study on the effect of magnesium sulfate infusion on the incidence and severity of emergence agitation in children under going adenotonsillectomy under sevoflurane anesthesia reported a 72% incidence of emergence agitation. (14). We presumed that a clinically significant difference would be 50% between the incidence of agitation in the intervention and control groups. With a power of 85% (a = 0.05, two-tailed), the sample size was calculated to be 93 patients (31 in each group). The sample size was calculated using Power Analysis and Sample Size 12 software (NCSS, Kay seville, ut USA).

Eligibility criteria: Inclusion Criteria:

-All participants undergoing lower abdominal surgeries

Exclusion Criteria:

All participants with:-

* history of developmental delay,
* mental retardation,
* psychological disorders or
* Epilepsy which can make observational pain intensity assessment difficult,
* a known or suspect coagulopathy,
* a known allergy to any of the study drugs and
* any signs of infection at the site of the proposed caudal block.

Primary outcomes:
measure: Number of Participants With sevoflurane-agitation are Assessed by Pediatric anesthesia emergency delirium scale (PAED) in 3 groups caudal versus intravenous magnesium sulfate infusions or caudal block alone
timeFrame: up to 96 weeks
Secondary outcomes:
measure: Number of Participants With Pain and its severity will be measured using FLACC in 3 groups caudal versus intravenous magnesium sulfate infusions or caudal block alone after inhalational sevoflurane anesthesia in children
timeFrame: up to 96 weeks
measure: The discharge from the post anesthetic care unit will be measured using Modified Aldrete score after inhalational sevoflurane anesthesia in children in 3 groups
timeFrame: up to 96 weeks
Other outcomes:
Locations:
city: Mansourah
country: Egypt
facility: Marwa ibrahim mohamed abdo
Study officials:
affiliation: Profosser of anesthesia and surgical intensive care
name: Gehan Ad Tarabeah, MD
role: STUDY_CHAIR
affiliation: Assisstant professor of anesthesia and surgical intensive care
name: Hesham Ah Abdel Mohaiemn, MD
role: STUDY_DIRECTOR
affiliation: Lecturer of anesthesia and surgical intensive care
name: Marwa Ib Abdo, MD
role: STUDY_DIRECTOR
affiliation: Resident of anesthesia and surgical intensive care
name: Mahmoud Mo Abdel latef, Ph.D
role: PRINCIPAL_INVESTIGATOR
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