Justification Of Empiric Methodology to Determine Dexmedetomidine Dose for the TREX Study.

INTRODUCTION: Dexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59-67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates. METHODS: The TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicentre, superiority trial comparing neurological outcome after standard sevoflurane anaesthesia with dexmedetomidine/remifentanil and low dose sevoflurane anaesthesia in children aged less than 2 years undergoing anaesthesia of 2 hours or longer. In this report, dexmedetomidine pharmacokinetics were analysed in the interventional arm of the Italian population. RESULTS: There were 162 blood samples from 32 infants (22 male and 10 female). The median (IQR) age was 12 (5.2-15.5) months, weight 9.9 (7.3-10.8) kg. Duration of anaesthesia ranged from 2-6 hours. None of the children were born premature (median postnatal age 39 weeks, IQR 38-40 weeks). A 3-compartment PK model that incorporated allometric scaling and a maturation function demonstrated plasma concentration observations from the current Italian arm of the TREX study were consistent with those predicted by a "universal" model using pooled data obtained from neonates to adults. CONCLUSIONS: This current PK analysis from the Italian arm of the TREX study confirms that plasma concentration of dexmedetomidine is predictable using known covariates such as age and size. The initial target concentration (0.6 µg.L-1 ) used to sedate children cared for in the intensive care after cardiac surgery was inadequate for infants in the current TREX study. A target concentration 1 mcg.L-1 , corresponding to a loading dose of 1 mcg.kg-1 followed by an infusion of 1 mcg.kg-1 .hour-1 , provided adequate sedation.

Complications associated with paediatric airway management during the COVID-19 pandemic: an international, multicentre, observational study.

Respiratory adverse events in adults with COVID-19 undergoing general anaesthesia can be life-threatening. However, there remains a knowledge gap about respiratory adverse events in children with COVID-19. We created an international observational registry to collect airway management outcomes in children with COVID-19 who were having a general anaesthetic. We hypothesised that children with confirmed or suspected COVID-19 would experience more hypoxaemia and complications than those without. Between 3 April 2020 and 1 November 2020, 78 international centres participated. In phase 1, centres collected outcomes on all children (age ≤ 18 y) having a general anaesthetic for 2 consecutive weeks. In phase 2, centres recorded outcomes for children with test-confirmed or suspected COVID-19 (based on symptoms) having a general anaesthetic. We did not study children whose tracheas were already intubated. The primary outcome was the incidence of hypoxaemia during airway management. Secondary outcomes included: incidence of other complications; and first-pass success rate for tracheal intubation. In total, 7896 children were analysed (7567 COVID-19 negative and 329 confirmed or presumed COVID-19 positive). The incidence of hypoxaemia during airway management was greater in children who were COVID-19 positive (24 out of 329 (7%) vs. 214 out of 7567 (3%); OR 2.70 (95%CI 1.70-4.10)). Children who had symptoms of COVID-19 had a higher incidence of hypoxaemia compared with those who were asymptomatic (9 out of 51 (19%) vs. 14 out of 258 (5%), respectively; OR 3.7 (95%CI 1.5-9.1)). Children with confirmed or presumed COVID-19 have an increased risk of hypoxaemia during airway management in conjunction with general anaesthesia.

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Preliminary results of video-assisted anal fistula treatment (VAAFT) in children.

BACKGROUND: Anal fistula is a common acquired anorectal disorder in children. Treatment methods that have been used are associated with inconsistent results and possible serious complications. In 2011 a minimally invasive approach, video-assisted anal fistula treatment (VAAFT) was described for adult patients. The aim of the present study was to assess the first series of pediatric patients treated with VAAFT. METHODS: All patients who underwent VAAFT between August 2013 and May 2015 were included. Demographics, clinical features, preoperative imaging, surgical details, outcome, and medium-term data were prospectively collected for each patient. RESULTS: Thirteen procedures were performed in nine patients. The male to female ratio was 8:1, and the median age was 9.6 years. Five fistulas were idiopathic, three iatrogenic, and one associated with Crohn's disease. Eight complete VAAFT procedures were performed. The remaining five procedures were either fistuloscopy and cutting seton placement or fistuloscopy and electrocoagulation, both without mucosal sleeve. The median length of surgery was 41 min. The median hospital stay was 24 h, and the median length of follow-up was 10 months. Resolution of the fistula was observed in all patients who underwent a complete VAAFT. In four out of five patients who underwent an incomplete procedure (without mucosal sleeve), the fistula recurred. No incontinence or soiling was reported in the medium term. CONCLUSIONS: VAAFT proved to be feasible and safe in children. It also proved to be versatile as it could be applied to fistulas of different etiologies. The key to success seems to be an adequate mucosal sleeve. Older children and adolescents benefit most from VAAFT which is a valid alternative to available surgical procedures.

Inguinal hernia in neonates and ex-preterm: complications, timing and need for routine contralateral exploration.

BACKGROUND/PURPOSE: Aim of this study was to present a series of neonates and ex-preterm babies who underwent inguinal hernia repair focusing on complications and possible indication to perform routine contralateral groin exploration. METHODS: This is a retrospective study of a series of consecutive patients weighing less than 5 kg who underwent inguinal hernia repair between January 2007 and December 2012. Only the affected side was treated. Patients have been routinely followed up postoperatively. We resorted to available outpatients' charts and admission notes to record demographic data, surgical details, complications and the occurrence of metachronous hernias. A questionnaire was administered to all patients' relatives to confirm the long-term outcome. RESULTS: One hundred fifty-four patients were operated for a total of 184 herniotomies (88 right sided, 36 left sided and 30 bilateral). Median length of follow-up was 42 months (range 6 months-7.5 years). Thirteen patients (13/124 = 10.5 %) developed metachronous hernia that proved to be significantly more frequent in patients weighing less than 1,500 g at birth (p < 0.05). We observed 10 % of complications, including 2.7 % testicular atrophy and 4.5 % recurrence. Atrophy proved to occur more frequently in patients who experienced preoperative incarceration (p < 0.05). No other risk factors were identified. CONCLUSIONS: The results of our series demonstrated that, though technically demanding, herniotomy in the neonate and ex-preterm is associated with a relatively low incidence of complications. Based on our results and in accordance with literature data, we do not advocate routine contralateral exploration in case of unilateral hernia but surgery to be performed only on the symptomatic side, as soon as possible after initial diagnosis. Very low birth weight patients should be followed with care in the early postoperative period due to the higher likelihood of developing a metachronous hernia.

Megacystis, megacolon, and malrotation: a new syndromic association?

Chronic intestinal pseudo-obstruction (CIPO) can occur as a consequence of neuropathies including diffuse Intestinal Neuronal Dysplasia (IND), a relatively rare enteric nervous system (ENS) abnormality. Although various authors reported of diffuse IND associated either with intestinal malrotation or megacystis, the co-existence of these three entities in the same patient has never been described before. The aim of this paper is to report for the first time in literature a series of patient with such association, focusing on one who carries a de novo duplication of chromosome 12, suggesting a new syndromic association (megacolon, megacystis, malrotation).

Methodologies for the treatment of acute and chronic nononcologic pain in children.

Pain represents the most feared symptom of illness but for many years it has been underestimated in children. Only recently has analgesic treatment become an integral part in the assistance of ill children with acute pain, such as postoperative pain, and with chronic pain. Postoperative pain is a complication of surgery: postoperative pain prevention should replace the current theory and practice of postoperative treatment through the creation of ''pain services'' and adequate pain prevention planning. Pain prevention begins in the preoperative period, continues in the operating theaters and in the postoperative phase. A multimodal approach should employ techniques of loco-regional anesthesia using a variety of agents from opioids to nonsteroidal anti-inflammatory drugs or paracetamol. The techniques we currently use to control procedural pain are both medical and nonmedical. Nonmedical interventions such as distraction, muscular relaxation, and guided imagination for pain control are psychological techniques showing very good results in those children who must undergo various procedures. The medical treatment must guarantee both sedation and effective analgesia. Our medical approach includes local anaesthesia, conscious sedation, deep sedation, and general anaesthesia.

Preoperative parental information and parents' presence at induction of anaesthesia.

Preoperative preparation of paediatric patients and their environment in order to prevent anxiety is an important issue in paediatric anaesthesia. Anxiety in paediatric patients may lead to immediate negative postoperative responses. When a child undergoes surgery, information about the child's anaesthesia must be provided to parents who are responsible for making informed choices about healthcare on their child's behalf. A combination of written, pictorial, and verbal information would improve the process of informed consent. The issue of parental presence during induction of anaesthesia has been a controversial topic for many years. Potential benefits from parental presence at induction include reducing or avoiding the fear and anxiety that might occur in both the child and its parents, reducing the need for preoperative sedatives, and improving the child's compliance even if other studies showed no effects on the anxiety and satisfaction level. The presence of other figures such as clowns in the operating room, together with one of the child's parents, is an effective intervention for managing child and parent anxiety during the preoperative period.

Propofol sedation with fentanyl or midazolam during oesophagogastroduodenoscopy in children.

BACKGROUND AND OBJECTIVE: Sedation is commonly used to facilitate diagnostic procedures in children. The aim of our study was to investigate sedation in children using propofol alone or combined with fentanyl or midazolam with regard to efficacy, adverse reactions or side-effects related to the drugs, ease of operation for the endoscopist, and time to discharge from the post-anaesthesia care unit. METHODS: We prospectively studied 240 children, aged 1-12 yr of age, undergoing endoscopic procedures of the upper gastrointestinal tract. The patients were given an oral premedication with midazolam (0.5 mg kg(-1)) and were then randomly allocated to one of the three study groups: propofol alone (Group P), propofol with fentanyl 1 mug kg-1 (Group PF) or propofol with midazolam 0.1 mg kg(-1) (Group PM). Additional doses of propofol given during the procedure were recorded. Adequacy of sedation and ease of procedure (easy, adequate, impossible) were evaluated by the endoscopist, who was blinded as to the drugs used. RESULTS: The duration of the procedure and the recovery period were similar in the three groups. The number of patients requiring supplemental doses of propofol to permit safe completion of gastroscopy was 31 in Group P (=39%; eight of these required two additional doses), 14 in Group PM (=18%), and 11 in Group PF (=13%) (P < 0.05). There was a lower incidence of adverse events in Group PM and in Group PF than in Group P (P < 0.05). CONCLUSIONS: Propofol in combination with fentanyl or midazolam gives better sedation and ease of endoscopy than propofol alone.

Levobupivacaine 0.25% compared with ropivacaine 0.25% by the caudal route in children.

BACKGROUND AND OBJECTIVE: Levobupivacaine is the most recently introduced local anaesthetic into clinical practice. In a randomized double-blinded study, the onset, intraoperative tolerance, postoperative analgesic effect, motor blockade and any adverse reactions produced by levobupivacaine were compared with ropivacaine. METHODS: Sixty children, ASA I-II, 2-6 yr old, undergoing elective minor surgery, received a single caudal injection of 1 mL kg(-1) of either levobupivacaine 0.25% or ropivacaine 0.25%. Caudal blocks were performed after induction of inhalation general anaesthesia using sevoflurane; anaesthesia was maintained via a laryngeal mask airway using a mixture of sevoflurane, oxygen and air. RESULTS: Onset time, intraoperative tolerance, postoperative analgesic effect and motor blockade were comparable between the two groups. The mean onset of the block was 8.2 +/- 2.2 min for levobupivacaine and 8.5 +/- 3.0 min for ropivacaine (P = 0.66). Additional analgesics during operation were not required in any of the children. No significant difference was found for mean time to requirement of additional analgesia with rectal acetaminophen (paracetamol) (302 +/- 29 min for the levobupivacaine group and 230 +/- 38 min for the ropivacaine group (P = 0.32)). During the first 4 h after placement of caudal block, the pain assessment score (according to the Children Hospital Eastern Ontario Pain Scale) was comparable for the two groups. No motor block was observed in any group on awakening, nor during the observation period. CONCLUSIONS: We conclude that levobupivacaine 0.25% 1 mL kg(-1) provides caudal block of comparable onset and duration, as produced by the same volume and concentration of ropivacaine.

One-stop surgery in pediatric surgery. Aspects of anesthesia. Preliminary report.

AIM: One-Stop Surgery (OSS) is a new day surgery combining preoperative evaluation and subsequent operation in one medical examination. METHODS: This paper reports the authors' initial experience using this method. Referring physicians were informed of the methods and selected surgical and anesthetic procedures by fax. They were also faxed a form to fill in with case history details and instructions to the parents on the preoperative fast. The completed form was faxed back to the surgeon and pediatric anesthetist who determined patient suitability and scheduled hospitalization and surgery. On hospitalization physical examination was performed to confirm diagnosis and rule out contraindications for anesthesia. Patients considered suitable then underwent surgery and were discharged on the same day as a day case. The families were given instructions to be followed for home care and emergency telephone numbers. In the time interval November 2000 to February 2001 43 patients aged between 2 and 7 years were treated following this procedure for removal of a central venous catheter (16 patients), umbilical (2 patients) and inguinal (10 patients) hernia repair, and prepuce dorsal slit (15 patients). Anesthesia consisted of nasal premedication using midazolan, general inhalation anesthesia and peripheral locoregional block. RESULTS: The diagnosis of all chidren was confirmed. Only 1 patient with upper airway infection was discovered. Recovery of all patients was uneventful. None of the patients called during the postoperative follow-up period for adverse events. CONCLUSIONS: Low costs and major parent and patient satisfaction are the main advantages of OSS, while the possible disadvantages are inaccurate referral for surgery and detection of contraindications for anesthesia at admittance to hospital. The authors recommend the use of wide scale OSS only when the operators have sound experience in pediatric day surgery.

Two doses of oral ketamine, given with midazolam, for premedication in children.

BACKGROUND: Oral premedication is common practice in paediatric anaesthesia. The aim of this study was to assess the quality of premedication using oral ketamine, with midazolam. METHODS: Clinical randomized and blind-study on 120 patients, aged between 2 and 6 years, listed for minor surgery. Patients were divided in three groups: first group (group MK1) received midazolam and ketamine at the doses of 0.3 mgxkg-1 and 1 mgxkg-1, respectively; the second (group MK2) received 0.3 mgxkg-1 of midazolam and 2 mgxkg-1 of ketamine; the control group 0.5 mgxkg-1 of midazolam (group M). Success of premedication was assessed by assigning 1-4 points to the quality of anxiolysis and sedation every 5 min after drug administration and then at the moment of separation from parents, entrance to theatre and response to mask induction of general anaesthesia. RESULTS: More patients were successfully premedicated in the MK2 group, statistical significance was observed after 20 min (p<0.05). The MK2 group accepted separation from parents (p<0.05) and face mask for induction of anaesthesia (p<0.05) more willingly. Side effects were observed in 4 MK2 group patients (nausea, headache and diplopia), but all these effects resolved spontaneously. CONCLUSIONS: Two mgxkg-1 of ketamine given orally with midazolam improve anxiolysis and sedation and achieve more success of premedication, better acceptance of parental separation and better acceptance of face mask for induction of anaesthesia.

Developments in the treatment of postoperative pain in paediatrics.

Although appreciation of pain has long been ignored, and even denied, in children its prevention and treatment is now an integral part of standard patient management. The current state of strategies of pain management in infants and children are detailed in this article and we focused on new trends and future developments.