Petra M. Meier

Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-blind, Placebo-controlled Trial

Background:Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively. Methods:Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg−1, followed by an infusion of 5 mg·kg−1·h−1 during surgery. TXA plasma concentrations were measured. Results:The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg−1, P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg−1, P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg−1 (95% CI for the difference, 23–84 ml·kg−1) and for packed erythrocytes transfused was 23 ml·kg−1 (95% CI for the difference, 7–39 ml·kg−1). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 &mgr;g·ml−1) and plasmin-induced platelet activation (16 &mgr;g·ml−1) throughout the infusion. Conclusions:TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents

Quantitative sensory testing (QST) is a noninvasive, computer‐assisted method for assessing function in peripheral small and large sensory fibers. In order to use QST for clinical neurological assessment in children, it is necessary: (1) to determine whether children can reliably perform these tests and (2) to characterize normal ranges in healthy children. Values of cold sensation, warm sensation, cold pain, heat pain, and vibration sensation detection thresholds were determined in the hand and foot with the method of limits (MLI) and method of levels (MLE) in 101 healthy children aged 6–17 years using a commercially available device. Both MLI and MLE were well‐accepted by children, and there was good reproducibility between two sessions. The MLE takes longer to perform but produces lower thermal detection thresholds than the MLI. In the MLI, vibration and warm sensation showed higher thresholds in the foot than hand, whereas cold pain showed lower thresholds in the foot than hand. Based on these results, QST may be used to document and monitor the clinical course of sensory abnormalities in children with neurological disorders or neuropathic pain.

Robotic Assisted Laparoscopic Ureteral Reimplantation in Children: Case Matched Comparative Study With Open Surgical Approach

PURPOSE Surgical treatment may be required in some patients with vesicoureteral reflux. With the recent development of robotic assistance, laparoscopic treatment of vesicoureteral reflux has gained popularity. We sought to evaluate our initial experience with pediatric robotic assisted laparoscopic intravesical and extravesical ureteral reimplantation, and to compare outcomes with the open technique. MATERIALS AND METHODS A retrospective chart review was performed on all patients who underwent robotic assisted laparoscopic ureteral reimplantation between 2007 and 2010. Comparisons were made with a case matched cohort of patients who underwent the open technique. The groups were compared using t tests for numerical variables and chi-square comparisons or Fishers exact test for categorical variables. A Kaplan-Meier model was used to compare success rates. RESULTS A total of 19 patients underwent intravesical and 20 underwent extravesical robotic assisted laparoscopic ureteral reimplantation during the study period. They were compared to 22 patients undergoing intravesical and 17 undergoing extravesical open ureteral reimplantation. Although the robotic assisted approach was associated with a longer operative time (p <0.001), children undergoing intravesical robotic assisted reimplantation had a shorter duration of urinary catheter drainage, fewer bladder spasms and a shorter hospital stay compared to those undergoing the intravesical open technique (p <0.01). There were no significant differences in these parameters when comparing extravesical robotic assisted reimplantation to the extravesical open technique. Overall success rates were similar among patients who underwent robotic assisted laparoscopic ureteral reimplantation and open reimplantation (p >0.5). CONCLUSIONS Robotic assisted laparoscopic ureteral reimplantation offers similar success rates to the gold standard, open ureteral reimplantation. Future large scale studies will be required to define further the costs and benefits of robotic assisted laparoscopic ureteral reimplantation in the surgical treatment of vesicoureteral reflux.

Long-term experience and outcomes of robotic assisted laparoscopic pyeloplasty in children and young adults.

PURPOSE Laparoscopic pyeloplasty is one of the more common robotic assisted procedures performed in children. However, data regarding long-term experience and clinical outcomes for this procedure are limited. We evaluated the long-term outcomes in a large series of patients undergoing robotic assisted laparoscopic pyeloplasty at a teaching institution, and the effect of a collaborative program between the robotic surgeons, surgical nurses and anesthesiologists on overall operative time. MATERIALS AND METHODS We retrospectively reviewed 155 patients who underwent robotic assisted laparoscopic pyeloplasty between 2002 and 2009. Operative data, including surgical approach, type of procedure, total and specific operative times and placement of ureteral stents, were determined. Postoperative outcome measurements, including duration of hospital stay, duration of Foley catheter drainage, radiological findings and any subsequent complications, were assessed. RESULTS Mean operative time and length of hospitalization decreased significantly by the end of the study. At a mean followup of 31.7 months the primary success rate was 96% (hydronephrosis was improved in 85% of patients and stable in 11%). The complication rate was 11%, and recurrent obstruction requiring redo robotic assisted laparoscopic pyeloplasty or open pyeloplasty developed in 3% of patients. Success rate and complication rate were unchanged during the study period. CONCLUSIONS This study confirms that even within the confines of a pediatric urology training program successful collaboration between robotic surgeons, surgical nurses and anesthesiologists can lead to shorter operative times and hospital stays. Long-term surgical success and complication rates were comparable to open surgery.

Cutaneous sensory abnormalities in children and adolescents with complex regional pain syndromes

Abstract Complex regional pain syndromes (CRPS) have been recognized with increasing frequency in children. These disorders appear to differ markedly from those observed in adults. The International Association for the Study of Pain diagnostic criteria for CRPS were developed based on adult studies; these criteria have not been validated for children. We performed standardized neurological examination and quantitative sensory testing (QST) in a group of pediatric patients to characterize features of sensory dysfunction. Forty‐two patients, with unilateral lower extremity CRPS of a mean duration of the pain and symptoms of 12.6 months, who met IASP adult‐based criteria for CRPS underwent standardized neurological examination and QST. QST parameters were compared to values previously derived from age‐ and sex‐matched pediatric healthy controls. In most respects, QST parameters did not differ significantly between patients and the normal reference values except for cold and heat pain detection thresholds. Allodynia to cold and/or heat (P < 0.001) occurred in 21 patients. Cold allodynia was the most common QST abnormality in our patients. Twenty‐six patients showed a combination of mechanical dynamic and static allodynia and allodynia to punctate temporal summation. There was a significant correlation between mechanical dynamic allodynia and allodynia to punctate temporal summation (P < 0.001). As with adult CRPS, the thermal and mechanical sensory abnormalities appear in different combinations in different patients with similar clinical presentations. In a majority of patients, the pathogenesis of pain is seemingly of central origin.

Lumbar sympathetic blockade in children with complex regional pain syndromes: a double blind placebo-controlled crossover trial.

Background:Sympathetic blockade is used in the management of complex regional pain syndromes in children, but there are no data on the efficacy or mechanism(s) by which it produces pain relief. The purpose of this study is to compare the efficacy of lidocaine administered by lumbar sympathetic to IV route. Methods:Under general anesthesia, children with unilateral lower limb complex regional pain syndromes received catheters along the lumbar sympathetic chain. In a double-blind placebo-controlled crossover design, patients received IV lidocaine and lumbar sympathetic saline or lumbar sympathetic lidocaine and IV saline. Spontaneous and evoked pain ratings and sensory thresholds were assessed before and after these two lidocaine/saline doses and between routes of lumbar sympathetic blockade and IV. Results:Twenty-three patients, ages 10–18 yr, were enrolled. There was evidence for reduction of mean pain intensity of allodynia to brush (mean –1.4, 95% confidence interval [CI] –2.5 to –0.3) and to pinprick temporal summation (mean –1.3, 95% CI –2.5 to –0.2) with lidocaine treatment via the lumbar sympathetic blockade compared to IV route. Lumbar sympathetic blockade also produced significant reduction in pain intensity compared to pretreatment values of allodynia to brush, pinprick and pinprick temporal summation and verbal pain scores. IV lidocaine did not produce significant changes in spontaneous and evoked pain intensity measurements compared to pretreatment values. There were no carryover effects as assessed by route-by-period interaction. Conclusions:Under the conditions of this study, the results provide some direct evidence that a component of pain may be mediated by abnormal sympathetic efferent activity.

Endoscopic strip craniectomy in early infancy: the initial five years of anesthesia experience.

BACKGROUND:Minimally invasive endoscopic strip craniectomy (ESC) is a relatively new surgical technique for treating craniosynostosis in early infancy. In this study we reviewed our anesthesia experience with ESC. The hypothesis was that infants with low body weight and syndromes would have a higher risk of perioperative blood transfusion and that those with respiratory complications are more likely to be admitted to the intensive care unit (ICU). METHODS:We retrospectively reviewed patient charts and anesthesia records of the first 100 consecutive infants who underwent ESC between May 2004 and December 2008 and follow-up evaluations until December 2009. Outcomes included (a) perioperative blood transfusion, (b) venous air embolism (VAE), (c) ICU admission, and (d) reoperation with craniofacial reconstruction procedures. Multivariable logistic regression was used to determine significant factors of patient outcomes. RESULTS:Infants ranging from 4 to 34 weeks of age (weight: 3.2 to 10.1 kg), presented for 87 single and 13 multiple ESC. Four infants had a craniofacial syndrome. The mean surgical time was 48 minutes (range: 26 to 86 minutes). Ninety-two infants had a median estimated blood loss of 23 mL (interquartile ranges [IQR]: 15 to 30 mL). Eight infants who required blood transfusion received a median amount of 17.2 mL/kg (IQR: 10.1 to 21.2 mL/kg). Body weight ⩽5 kg (P = 0.04), sagittal ESC (P < 0.01), syndromic craniosynostosis (P < 0.01), and earlier date of surgery in the series (P < 0.01) were factors associated with blood transfusion. VAE was detected in 2 infants with no changes in clinical outcome. Eight infants were admitted to the ICU. Factors associated with ICU admission were blood transfusion (P < 0.001) and respiratory complications (P < 0.001). Eighty-two infants were discharged on postoperative day 1 (range: 1 to 3 days). Six infants underwent subsequent fronto-orbital advancement and 1 cranial vault reconstruction. Multiple-suture craniosynostosis (P < 0.01), associated syndromes (P = 0.03), and ICU admission after ESC (P = 0.04) were predictive of reoperation. CONCLUSIONS:Twenty percent of infants undergoing ESC had 1 or more of the following: need for blood transfusion, VAE, respiratory complications, and ICU admission. Multivariable analysis confirmed that patients with lower body weight, those with earlier date of surgery in the series, those undergoing sagittal ESC, and those with syndromic craniosynostosis had a higher rate of blood transfusion. ICU admissions often occurred in infants requiring transfusion and those with respiratory complications. Infants with multiple-suture craniosynostosis were more likely to require subsequent craniofacial reconstruction procedures.

The effectiveness of aerosolized intraperitoneal bupivacaine in reducing postoperative pain in children undergoing robotic-assisted laparoscopic pyeloplasty

OBJECTIVE To assess the effectiveness of aerosolized intraperitoneal bupivacaine in reducing postoperative pain in children. Laparoscopic surgery has decreased the severity of postoperative pain in children. However, children often experience abdominal and shoulder pain requiring significant amounts of opioids, potentially prolonging their hospitalization. METHODS Forty-one consecutive patients undergoing unilateral robotic-assisted pyeloplasty between December 2005 and December 2007 were retrospectively reviewed to assess perioperative opioid requirements and length of hospitalization. RESULTS In addition to standard-of-care perioperative analgesia, five patients received intraperitoneal aerosolized bupivacaine just prior to trocar removal, 17 patients received aerosolized bupivacaine just prior to incising the perirenal fascia, and 19 patients received no intervention. There was a significant reduction in postoperative opioid utilization when bupivacaine was administered at the beginning of the surgery (0.1mg/kg vs 0.4mg/kg, P=0.04), but not at the end (0.3mg/kg, P=0.25), as compared to controls. All patients receiving aerosolized bupivacaine had a significantly shorter time in hospital (2.4 vs 1.4 days, P=<0.01). CONCLUSIONS The administration of intraperitoneal aerosolized bupivacaine just prior to incising the perirenal fascia appears to be a simple, effective and low-cost method to reduce postoperative pain in children undergoing laparoscopic pyeloplasty.

Pain hypersensitivity in juvenile idiopathic arthritis: a quantitative sensory testing study

BackgroundJuvenile Idiopathic Arthritis (JIA) is the most common cause of non-infectious joint inflammation in children. Synovial inflammation results in pain, swelling and stiffness. Animal and adult human studies indicate that localized joint-associated inflammation may produce generalized changes in pain sensitivity. The aim was to characterize pain sensitivity in children with JIA to mechanical and thermal stimulus modalities using quantitative sensory testing (QST) at an affected inflamed joint, and compare to children in clinical remission. Generalized hypersensitivity was evaluated by comparing QST measures at the thenar eminence between JIA and healthy control children.Methods60 children aged 7–17 years with JIA participated. QST assessed sensory detection threshold and pain threshold at two sites: (1) affected joint (clinically active or inactive), (2) contralateral thenar eminence. Joint site included finger, wrist, knee and ankle. Clinical status was measured using objective and subjective markers of disease severity. Questionnaires assessed pain intensity and frequency, functional disability, anxiety, pain catastrophization and fatigue. QST data collected from joints were compared within JIA patients: active vs. inactive inflammation; and data from the contralateral thenar eminence were compared between JIA and healthy control cohorts in Europe [EU, (n = 151)] and the US (n = 92). Statistical analyses were performed using Kruskal-Wallis with Dunn’s post-hoc comparison, Mann-Whitney or Fisher’s exact test, where appropriate.ResultsOverall, children with JIA reported low pain scores and low degrees of functional disability. Sensory detection thresholds and pain thresholds were similar in “active” compared to “inactive” joints. Despite this, children with JIA had generalized hypersensitivity at the thenar eminence when compared to healthy children for pressure (vs. EU p < 0.001), light touch (vs. EU p < 0.001), cold (vs EU, p < 0.01; vs US, p < 0.001) and heat pain (vs EU, p < 0.05; vs US p < 0.001).ConclusionsJIA is associated with increased sensitivity to painful mechanical and thermal stimuli, even in absence of pain reports, or markers of disease activity. Future research investigating mechanisms underlying pain hypersensitivity in JIA is warranted; this will in turn guide pharmacologic and non-pharmacologic interventions to prevent or reverse these processes.

Predictors of clinically significant postoperative events after open craniosynostosis surgery.

Background: Craniosynostosis surgery is associated with clinically significant postoperative events requiring intensive care unit (ICU) admission. The authors investigate specific variables, which might influence the risk for these events, and thereby make recommendations regarding the need for postoperative ICU admission. Methods: A retrospective review of 225 children undergoing open craniosynostosis repair at a single center during a 10-yr period is reported. The primary outcome measure was the incidence of predefined clinically relevant postoperative cardiorespiratory and hematological events requiring ICU admission. Results: The incidences of postoperative cardiorespiratory and hematological events requiring ICU care were 14.7% (95% CI, 10.5 to 20.1%) and 29.7% (95% CI, 24.0 to 36.3%), respectively. Independent predictors of cardiorespiratory events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, and the occurrence of an intraoperative complication. The independent predictors of hematological events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, transfusion of hemostatic products (fresh-frozen plasma, platelets, and/or cryoprecipitate), and tranexamic acid not administered. Conclusions: Children undergoing craniosynostosis surgery are at increased risk for clinically significant postoperative events requiring ICU admission if they are less than 10 kg body weight, American Society of Anesthesiologists physical status 3 or 4, require intraoperative transfusion of greater than 60 ml/kg of packed erythrocytes, receive hemostatic blood products, or if they develop a significant intraoperative complication. Tranexamic acid administration was associated with fewer postoperative events. A predictive clinical algorithm for pediatric patients having major craniosynostosis surgery was developed and validated to risk stratify these patients.