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Biomedical subjects

Douglas G Ririe

Publications and source records attributed to Douglas G Ririe.

12 recordsLinked to original sources

Age-dependent responses to nerve injury-induced mechanical allodynia.

BACKGROUND: Developmental differences in responses to acute and chronic nerve injury have received minimal attention. This study examines developmental differences in behavioral responses to a proximal (closer to the spinal cord) (L5 and L6 spinal nerve root ligation) or to a more distal (closer to peripheral innervation) (partial sciatic nerve ligation) nerve injury in rats paralleling the infant to young adult human. METHODS: Withdrawal thresholds to von Frey filament testing in the hind paw were determined before and various times after either spinal nerve root ligation or partial sciatic nerve ligation in rats aged 2, 4, and 16 weeks. Control rats of these ages were observed serially without surgery. Times for withdrawal thresholds to mechanical stimuli to return to 80% of that of the hind paw in the control animals were compared among the different ages in the two models. RESULTS: Baseline withdrawal thresholds in younger rats were lower (P < 0.05). In the 2-week-old animals, distal injury partial sciatic nerve ligation did not cause a reduction in withdrawal threshold from baseline. This was different from the spinal nerve root ligation group and the older animals in the partial sciatic nerve ligation group. However, when compared with age-matched control animals, both nerve injuries resulted in reduced withdrawal thresholds (P < 0.05). The resolution of hypersensitivity to mechanical stimulation, as measured by return of threshold to 80% of controls, occurred more quickly in 2-week-old than in 4- and 16-week-old animals in both injury models (P < 0.05). CONCLUSION: These data suggest that resolution of sensitization to A-fiber input occurs more rapidly in young animals. In addition, distal injury has less of a sensitizing effect on A-fiber input than proximal injury in the younger animals. The authors speculate that neuroimmune responses, especially at the site of injury, are developmentally regulated and less likely to produce chronic pain when injury occurs at a young age.

Aging↗

Developmental differences in spinal cyclooxygenase 1 expression after surgical incision.

BACKGROUND: Systemic administration of a cyclooxygenase 1 (COX-1) inhibitor reduces hypersensitivity to mechanical stimuli after incisional paw surgery in 4-week-old, but not 2-week-old, animals. The purpose of the current study was to test whether this developmental difference was reflected by differences in COX-1 expression in the spinal cord after surgery. METHODS: Rats 2 and 4 weeks of age, paralleling infant and child human neurologic developmental stages, were used. A paw incision was made under general anesthesia and the withdrawal thresholds were measured before and after systemic and intrathecal administration of a COX-1 selective inhibitor (SC560). Immunohistochemistry was used to assess COX-1 protein in the spinal cord, and real-time polymerase chain reaction was used to quantify gene expression of COX-1 mRNA. RESULTS: Systemic and intrathecal administration of SC560 produced an increase in withdrawal threshold in the 4-week-old, but not in the 2-week-old, animals. Intrathecal SC560 increased withdrawal thresholds in the 4-week-old animals at a dose 100-fold less than with systemic administration. Cyclooxygenase 1 protein in the spinal cord was increased ipsilateral to surgery in the 4-week-old, but not in the 2-week-old, animals. Cyclooxygenase 1 mRNA was increased in the 4-week-old animals in the spinal cord ipsilateral to surgery relative to the contralateral side of the spinal cord, but not in the 2-week-old animals. CONCLUSIONS: These results suggest that developmental differences in COX-1 expression in the spinal cord likely explain the lack of efficacy of COX-1 inhibitors in the 2-week-old rats. Whether this reflects a deficit in factors that stimulate COX-1 expression or a difference in response to these factors is not addressed, but should similar deficits occur in humans, COX-1 inhibitors may exhibit reduced efficacy in infants.

Age Factors↗

Transfusion-related acute lung injury in an infant during craniofacial surgery.

UNLABELLED: Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, systemic, immune-mediated reaction to transfused blood product. The symptoms may be masked under general anesthesia. In this case report, we describe an infant who developed TRALI under general anesthesia for craniofacial surgery. The difficulty with diagnosis, the pathophysiology, and the need for understanding and recognition to reduce morbidity and mortality are discussed. IMPLICATIONS: Transfusion-related acute lung injury (TRALI) is a life-threatening problem that can occur during blood product transfusion in patients of any age. Understanding the pathophysiology may help make an earlier diagnosis to reduce more serious adverse outcomes.

Craniosynostoses↗

The antinociceptive effects of spinal cyclooxygenase inhibitors on uterine cervical distension.

Pain during labor is common and severe, as is menstrual pain, and this pain originates from the uterine cervix and is transmitted via the hypogastric nerve to the spinal cord. Prostaglandins play an important role in nociceptive transmission in the spinal cord. Pharmacologically, targeting a specific cyclooxygenase (COX) enzyme isoform has as its goal to effectively treat pain while avoiding side effects. Both COX-1 and COX-2 inhibitors have been shown to effectively treat a variety of pain conditions in animals and in humans; however, their efficacy in treatment of acute visceral pain has not been explored. The purpose of this study is to evaluate the pharmacologic effects of specific spinal COX inhibitors on uterine cervical distention induced nociception. The results indicate that intrathecal (i.t.) administration of the COX-2 inhibitor, SC58238, and the nonspecific COX inhibitor, indomethacin, effectively inhibited the electromyographic activity induced by UCD. None of the inhibitors altered hemodynamic response to uterine cervical distension. The study suggests that targeting spinal COX-2 could be useful to treat transient and acute visceral pain from the uterine cervix.

Analgesics↗

Preoperative sciatic nerve block decreases mechanical allodynia more in young rats: is preemptive analgesia developmentally modulated?

Postoperative sensitivity to tactile stimuli differs as a function of age. In this study, we hypothesized that preoperative sciatic nerve block (SNB), by providing preemptive analgesia, would result in better analgesia than postoperative SNB in the young rat. With the paw incision model of postoperative pain, male Sprague-Dawley rats, aged 2 or 4 wk, underwent general anesthesia and then received a left SNB with 5 microL/g of 0.5% bupivacaine or normal saline. SNB was performed either before or after surgery. Mechanical allodynia was assessed by using von Frey filaments before and at various times after SNB and surgery. In the 2-wk-old rats, preoperative SNB produced a significant reduction in mechanical allodynia, as reflected by a higher threshold at 2, 5, and 24 h when compared with saline control (P < 0.03). At 24 h, the threshold was 4.0 +/- 0.7 g in the preoperative SNB group compared with 1.6 +/- 0.3 g in the postoperative SNB group (P = 0.004). There was no difference at any time point between the preoperative and the postoperative SNB in the 4-wk-old animals. These results suggest that preoperative SNB in young animals provides a preemptive analgesic effect on mechanical allodynia that is age or developmentally dependent.

Aging↗

Video-assisted ductal ligation in premature infants.

BACKGROUND: Video-assisted thoracic surgery has been shown to be a safe and effective method of closing the patent ductus arteriosus in infants and children. We have applied this technique in low birth weight premature infants and now report our experience. METHODS: Since 1996, we have used video-assisted thoracic surgery ligation as the treatment of choice for all patent ductus arteriosus, including 100 performed on premature infants (23 to 31 weeks' gestation, mean 25.6 weeks; 0.420 to 1.5 kg, mean 0.859 kg). A modification of our previously described technique was used with a three-port approach. All patients had some degree of symptoms of congestive failure with failure to wean from ventilatory support or oxygen dependency. Five infants had associated patent foramen, and 1 had a small ventricular septal defect. RESULTS: All 100 procedures were performed in the operating room. One infant was found to have a coarctation, and the procedure was aborted. The remaining 99 were successfully ligated, although three were converted to an open procedure (3%) because of coagulopathy, poor pulmonary compliance, or hemodynamic instability. There were no procedure-related deaths; however, 15 infants subsequently died of complications of prematurity, including enterocolitis, sepsis, and late respiratory failure. Six infants had chest tubes left in place for coagulopathy, effusions, suspected air leak, and existing empyema. There were six residual pneumothoraces, four requiring treatment. CONCLUSIONS: Video-assisted thoracic surgery is a safe and effective technique for patent ductus arteriosus ligation in premature infants, including those with very low and extremely low birth weight.

Cohort Studies↗

Age-dependent responses to thermal hyperalgesia and mechanical allodynia in a rat model of acute postoperative pain.

BACKGROUND: Developmental differences in short- and long-term responses to pain, especially surgical pain, have received minimal attention. The purpose of the present study was to examine postoperative responses in rats of developmental ages paralleling the infant to young adult human. METHODS: The withdrawal threshold to von Frey filament testing and withdrawal latency to hind-paw radiant heating were determined before and for various times after hind-paw incision in rats 2, 4, and 16 weeks of age. Control rats of these ages were observed serially without surgery. RESULTS: In control animals, younger rats were more sensitive to mechanical stimulation and less sensitive to thermal stimulation. Paw incision resulted in similar changes to both types of stimulation in all age groups, peaking 4 h after surgery. However, the return to normal sensitivity to mechanical stimulation, as measured by return of threshold to 80% of normal, occurred more quickly in 2-week-old than in 4- and 16-week-old animals. In contrast, there was no age difference for time to return to normal sensitivity to thermal stimulation after surgery. CONCLUSIONS: The more rapid recovery of the younger animals from the mechanical allodynia but not thermal hypersensitivity after surgery suggests the presence of developmental differences in modulation of A-fiber sensitization after surgery. However, the lack of age difference in recovery of thermal hypersensitivity after surgery suggests that sensitization of C-fiber input has a similar time course of resolution of pain over the ages studied in this model. The neural bases for these developmental differences are under study and may lead to a better understanding of pain during development and altered approaches to treatment of postoperative pain in neonates and infants.

Acute Disease↗

Surgical advancement influences perioperative care: a comparison of two surgical techniques for sagittal craniosynostosis repair.

Methods for surgical correction of sagittal craniosynostosis have progressed. The hypothesis is that advances in surgical interventions for craniosynostosis affect perioperative anesthetic care. We reviewed the records of eight children who underwent cranial vault reconstruction (CVR) and nine who underwent spring-mediated cranial expansion (SME) for sagittal craniosynostosis. We compared the data from the CVR procedure to data from the combined procedures for SME (insertion and removal of springs). Anesthesia times were similar between the CVR (4 h 24 min) and the combined SME (4 h 27 min) groups, whereas surgical times were different between the CVR (3 h 25 min) and combined SME groups (2 h 21 min) (P = 0.002). Length of stay was 4.1 days for the CVR group (confidence interval [CI], 3.8-4.4 days) versus 3.1 days (CI, 2.9-3.4 days) in the combined SME group (P = 0.0001). Blood loss was significantly less in the combined SME group at 48 mL (CI, 29-83 mL) compared with the CVR group at 291 mL (CI, 230-352 mL). All eight patients in the CVR group received blood with a mean of 1.4 U (range, 1-2 U). No SME patient received any blood products. The reduction in blood loss with this new surgical treatment is significant for the patient in reducing blood transfusion and for the anesthesiologist in reducing concerns of volume resuscitation.

Adolescent↗

The pharmacokinetics of epsilon-aminocaproic acid in children undergoing surgical repair of congenital heart defects.

UNLABELLED: epsilon-Aminocaproic acid (epsilonACA) is often administered to children undergoing cardiac surgery by using empiric dosing techniques. We hypothesized that children would have different pharmacokinetic variables and require a dosing scheme different from adults to maintain stable and effective serum epsilonACA concentrations. Eight patients were enrolled in our study. epsilonACA 50 mg/kg was administered three times IV: before, during, and after cardiopulmonary bypass (CPB). Nine serum samples were obtained. epsilonACA plasma concentrations were measured by using high-performance liquid chromatography, and pharmacokinetic modeling was done by using NONMEM. The best fit was seen with a two-compartment model with volume of distribution (V(1)) adjusted for weight and CPB. Compared with published results in adults, modeling suggests that weight-adjusted V(1) is larger in children than in adults before, during, and after CPB. Clearance from the central compartment (k(10)) was also greater in children than adults, and declined during CPB. Redistribution rates from the central compartment, k(12) and k(21), were greater in children and not affected by CPB. We modeled several different dosing regimens for epsilonACA based on the larger V(1), and higher redistribution and clearance variables. We conclude that, because of the developmental differences in pharmacokinetic variables of epsilonACA, when compared with adult patients, a larger initial dose and faster infusion rate as well as an addi-tional dose on CPB are needed to maintain similar concentrations. IMPLICATIONS: Pharmacokinetic modeling of epsilon-aminocaproic acid in children undergoing cardiac surgery suggests that there are developmental differences in pharmacokinetic variables. Based on these data, a dosing modification in children is suggested which may better maintain serum concentrations in children when compared with adults.

Aminocaproic Acid↗