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While many children with renal tumors require long term venous access (VA) for adjuvant chemotherapy, certainly not all do. This study develops and tests a VA decision tree (DT) to direct the placement of VA in patients with renal tumors.Utilizing data readily available at surgery a VADT was developed. The VADT was tested retrospectively by 2 independent reviewers on a historic cohort. The ability of the VADT to appropriately select which patients would benefit from VA placement was tested.160 patients underwent renal tumor surgery between 2005 and 2018. 70 (43.8%) patients met study criteria with median age of 45.1 months (range 1.1-224); 73% required VA. Using the VADT, VA placement was "needed" in 67.1% of patients and "deferred" in 32.9%. Interrater reliability was very high (kappa = 0.97, 95% CI 0.91-1, p 0.001). The sensitivity and specificity of the VADT to correctly decide on VA placement were 0.92 (0.8-0.98) and 1 (0.79-1). Using the VADT, no patient would have undergone unnecessary VA placement. In reality, 4.3% of patients had an unnecessary VA placed which required a subsequent removal.These preliminary data support the continued study of this VADT to guide intraoperative decisions regarding VA placement in patients with renal tumors.III - Study of diagnostic test.

Background Adjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer‐related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Methods and Results Peripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index ( LVET i) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min −1 , respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVT i was lower in cancer therapies compared to controls. Conclusions These data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure.

Cloacal anomalies are the most complex and severe form of congenital anorectal malformations (ARM) and urogenital malformations, and it has been well documented that increased severity of ARM leads to worse outcomes. While short-term data on persistent cloaca are available, a paucity of data on long-term outcomes exists, largely because of a lack of uniform terminology, inclusion with other ARM and evolution of the operative technique. On comprehensive review of the published literature on long-term urological outcomes in patients with cloacal anomalies, we found a significant risk of chronic kidney disease and incontinence, however, with improvements in surgical technique, outcomes have improved. Continence often requires intermittent catheterization and in some cases, bladder augmentation. The complexity of cloacal malformations and associated anomalies make long-term multidisciplinary follow-up imperative.

Oncologic outcomes in advanced testicular cancer (TC) depend on appropriate and timely care. Often this care is referred to tertiary academic medical centers (AMCs). The aim of this study was to compare oncologic outcomes of adolescent and young adult (AYA) patients with TC treated from the outset at an AMC to those whose care was initiated elsewhere with subsequent referral.An institutional TC database was reviewed, and those AYA patients initiating TC care either inside or outside an AMC were compared. Patients were classified as initiating care outside if they had any non-orchiectomy surgery, chemotherapy, or radiotherapy for TC outside an AMC.A total of 183 patients were reviewed, of whom 59 initiated TC care outside and 124 were managed initially at an AMC. Patients initiating care outside were more likely to have non-seminoma histology and more often presented with metastatic disease (Stage II [30.5%] or III [35.6%] vs. Stage II [19.4%] or III [19.4%]; p = 0.007). Lower 3-year event-free survival (EFS) was observed in those initiating treatment outside an AMC (60.6% vs. 78.7%; p = 0.027). However, on multivariate analysis adjusting for stage and histology, the location of initiating TC care was no longer significant (hazard ratio = 1.5, 95% confidence interval 0.8-2.9).AYA patients initially treated for TC in the community and subsequently referred to an AMC were initially observed to experience worse EFS than those who were managed at an AMC from the outset. However, on multivariate analysis, these findings were largely explained by referral bias, where AYA patients with advanced disease were more likely to be referred to AMCs.

The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V˙O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (ΔTOIΔ/V˙O2) and [HHb] (Δ[HHb]/ΔV˙O2) relative to ΔV˙O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V˙O2 and O2 delivery during exercise.

Enhanced recovery after surgery (ERAS) protocol is a set of peri-operative strategies to increase speed of recovery. ERAS is well established in adults but has not been well studied in children.The purpose of the current study was to establish the safety and efficacy of an ERAS protocol in pediatric urology patients undergoing reconstructive operations. It was hypothesized that ERAS would reduce length of stay and decrease complications when compared with historical controls.Institutional Review Board approval was obtained to prospectively enroll patients aged18 years if they had undergone urologic reconstruction that included a bowel anastomosis. ERAS included: no bowel preparation, administration of pre-operative oral carbohydrate liquid, avoidance of opioids, regional anesthesia, laparoscopy when feasible, no postoperative nasogastric tube, early feeding, and early removal of intravenous fluids (IVF). Recent (2009-2014) historical controls were propensity matched in a 2:1 ratio on age, sex, ventriculoperitoneal shunt status and whether the patient was undergoing bladder augmentation. Outcomes were protocol adherence, length of stay (LOS), emergency department (ED) visits, re-admission within 30 days, re-operations and adverse events occurring within 90 days of surgery.A total of 26 historical and 13 ERAS patients were included. Median ages were 10.4 (IQR 8.0-12.4) and 9.9 years (IQR 9.1-11), respectively (P = 0.94) (see Summary Table). There were no significant between-group differences in prior abdominal surgery (38% vs 62%), rate of augmentation (88% vs 92%) or primary diagnosis of spina bifida (both 62%). ERAS significantly improved use of pre-operative liquid load (P 0.001), avoidance of opioids (P = 0.046), early discontinuation of IVF (P 0.001), and early feeding (P 0.001). Protocol adherence improved from 8/16 (IQR 4-9) historically to 12/16 (IQR 11-12) after implementation of ERAS. LOS decreased from 8 days to 5.7 days (P = 0.520). Complications of any grade per patient decreased from 2.1 to 1.3 (OR 0.71, 95% CI 0.51-0.97). There were fewer complications per patient across all grades with ERAS. No differences were seen in emergency department (ED) visits, re-admissions and re-operations.Implementation improved consistency of care delivered. Tenets of ERAS that appeared to drive improvements included maintenance of euvolemia through avoidance of excess fluids, multimodal analgesia, and early feeding.ERAS decreased length of stay and 90-day complications after pediatric reconstructive surgery without increased re-admissions, re-operations or ED visits. A multicenter study will be required to confirm the potential benefits of adopting ERAS.

t f a a ibrin sealant, also known as “fibrin glue” and “fibrin issue adhesive,” is a natural or synthetic hemostatic gent derived from plasma coagulation proteins. It is sually a combination of fibrinogen (factor I), fibrintabilizing factor (factor XIII), thrombin (responsible or conversion of fibrinogen to fibrin in the presence f calcium chloride), and aprotinin (an inhibitor of brinolysis). Tissue adhesive has been defined as “any ubstance with characteristics that allow for polymerzation, holding tissues together or serving as a barrier o leakage.”1 Natural and synthetic fibrin sealants are he most effective tissue adhesives and hemostatic gents available to surgeons. The concept of applying lotting factors for hemostasis has been considered or almost 100 years. In 1909, fibrin was used for the rst time for hemostatic purposes by Bergel.2 As years assed, the biochemical and adhesive properties of brinogen became well known, leading to widepread use of “home-made” fibrin glue by surgeons. he combination of homologous fibrinogen and hrombin was used during World War II to improve kin graft adhesion in burn patients.3 Although iniially promising, this application was met with skepicism due to the possibility of transmission of viral epatitis. Further development in technology allowed ubstitution of human thrombin with bovine thromin, thereby reducing the risk of viral transmission. owever, use of first-generation bovine proteins leads o documented cases of iatrogenic coagulopathies econdary to the formation of factor V and thrombin nhibitors.4 In the 1970s, Matras and colleagues used utologous cryoprecipitate solutions in animals to erform nerve anastomosis and microvascular proce

Computed tomography (CT) scanning in the head and neck region has become an integral part of the preoperative evaluation of tumor in defining the full extent of anatomic involvement, and the relation of the tumor to vital vascular and neurologic structures. CT utilizes the same ionizing X rays as plain-film radiography, except the X-ray beam is a thin, collimated linear beam, single but more often multiple; in plain films, a single beam is used, which disperses outward. In CT, the beam attenuated by the object being studied then is detected by a crystal detector and converted to electric energy. In plain film, the attenuated beam then strikes a photoemulsion silver-based film, causing a photochemical reaction, which can then be processed into a photograph. Thus, the CT scan is not a real image of a real object, whereas the plain-film radiograph is. Basically, the object being studied casts a shadow (absorbs the X ray so that it does not penetrate to the film) of a real object. In CT, the final picture is a reconstructed computer simulation. Nevertheless, the simulation does accurately reflect the real anatomy. Unlike plain film, CT scanning takes thousands of small images and actual X-ray beam exposures compared with the one shot in plain film. Because the beam is so thin, however, the overall tissue absorption is about equal to, and sometimes less than, the amount of radiation exposure encountered in plain-film radiography. To generate a picture utilizing a matrix, there must be a way to spatially encode the thin X-ray beams of CT. This is accomplished in part by the rotating ring, with single, multiple, and radial beams, by incrementing in 1� intervals the X-ray tube and the crystal detectors around the object being studied, and taking pictures at each incremental rotation. In MR imaging, the spatial encoding is accomplished by applying small, linear, magnetic gradients, and thus frequency encoding, in the X direction, and phase encoding in the Y direction. The current CT technology then utilizes continual scanning but incrementing in a helical or spiral fashion to reduce further the CT scanning times, as opposed to the earlier scan utilizing one slice, stop, move table, and repeat. The latest technology places the crystal detectors in arrays or banks, rather than the linear-or circular-oriented single row of detectors. None of the new technologies increases anatomic resolution but instead reduces scanning times, which benefits CT angiography or cinefluoroscopic CT. The electric signal is then analyzed by Fourier transformation, which further adds information about spatial encoding. The spatially encoded electric signal, by means of back projection, can then be used to determine how bright or dark each pixel of the picture matrix should be. Resolution as high as a 1024 · 1024 matrix can then be created for temporal bone imaging. More often, a 512 · 512 matrix is used for most CT scanning of the head and neck. To generate a gray-scale image, a zero point needs to be established. CT intensity readings are assigned Hounsfield units (HUs), with the zero value representing water and cerebrospinal

Background The ability of intraoperative frozen section (IFS) to reliably diagnose renal tumors in children and adolescents is largely unknown. The objective of our study is to evaluate the ability of IFS to establish a histologic diagnosis for renal tumors in this population. Methods We reviewed our experience with patients who underwent IFS at the time of surgery for a renal tumor suspicious for malignancy from 2005 to 2015. The IFS was compared to the final pathology (FP). Data on concordance and reliability were analyzed. Results One hundred thirty patients underwent surgical interventions for a renal tumor suspicious for malignancy, and 32 (25%) patients underwent IFS. Median turnaround time for IFS was 20 min (range 13–44). The histologic IFS diagnosis correlated with FP in 26 (81.2%) cases was discrepant in three (9.4%) cases, and IFS was deferred to FP in three (9.4%) cases (kappa 0.71, 95% confidence interval [CI]: 0.52–0.899, P < 0.001). The IFS correctly distinguished between Wilms tumor and non-Wilms tumor in 30 (94%) cases (kappa 0.874, 95% CI: 0.705–1, P < 0.001). A total of 17 of 19 (89.5%) Wilms tumors were correctly diagnosed by IFS, yielding a sensitivity of 0.89 (95% CI: 0.67–0.99) and a specificity of 1 (95% CI: 0.75–1). Conclusion IFS is a reliable tool to establish a histologic diagnosis and to differentiate between Wilms and non-Wilms tumors in children and adolescents with renal tumors. The use of IFS should be encouraged in cases in which obtaining a diagnosis will provide guidance for important “real-time” medical decision making, specifically additional adjunctive surgical procedures.

Rats with 50% total body surface area full-thickness burn injuries have sustained increases in body temperature without evidence of sepsis. In this animal model, the only known endogenous pyrogen consistently present in plasma is interleukin-6 (IL-6). We investigated the hypothesis that IL-6 acts as an endogenous pyrogen and produces the observed increase in body temperature. Body temperature and activity index were recorded every 5 minutes for control rats and rats with burns (50% total body surface area scald burns) for a period before the burn injuries and through the eighth day after the burn injuries. On the fifth day after the burn injuries, between 8 and 9 AM, control animals and animals with burns were given an intra-arterial dose of IL-6 polyclonal neutralizing antibody (IL-6 pAb) that was equivalent to one half of the neutralizing dose of IL-6 pAb. This calculation was based on plasma levels of IL-6 obtained from rats with burns in previous studies and on the neutralizing capability of the IL-6 used. On the sixth and seventh days after the burn injuries, a full neutralizing dose of IL-6 pAb was given. Blood samples were obtained for IL-6 assays at baseline and after treatment with IL-6 pAb but were lost because of the failure of an ultracold freezer. A one half neutralizing dose of IL-6 pAb produced no discernible effect on the body temperature of the control animals or of the animals with burns. On the sixth and seventh days after the burn injury, IL-6 pAb produced 45% and 34% respective decreases in body temperature compared with the animals with burns that received saline solution (P < .05 for both comparisons). On the eighth day after the burn injuries, the effect had completely dissipated. We concluded that our results support the idea that increased circulating levels of IL-6 may be causally related to fever that occurs in nonseptic rats with large burn wounds.

Introduction: Rats with burn injury to ≥50% of the BSA demonstrate a significant increase in body temperature ( T B ) during light hours, and decrease of circadian variation in T B . This study investigated the hypothesis that part or all of the signal for increased T B in rats with burn injury is transmitted to the central nervous system by way of afferent vagal fibers. Methods: Four groups of animals were studied: Burn-Sham Vagotomy; Control-Sham Vagotomy; Burn-Vagotomy and Control-Vagotomy. Anesthetized animals had bilateral subdiaphragmatic vagotomy (VagX) or sham VagX performed, and AM radio transmitters were implanted in the peritoneal cavity for the purpose of recording T B and activity index (AI). Following a one week recovery period, burn animals received scald burns equal to 50.3±2.5% BSA. Results: The main effect of VagX upon T B was a small but significant reduction in T B during dark hours. At least 87% of this decrease in post-burn T B was also present for the control vagotomy group. Vagotomy had no effect on the increase in T B for the burn groups during light hours. During dark hours, VagX significantly reduced T B in burns and controls, and burn injury significantly reduced activity. Conclusions: One may speculate that afferent vagal signals are partially responsible for maintenance of T B , with or without burn injury, and that the major signal for increase in T B for animals with burn injury is not a neural one via afferent vagal pathways.

Purpose: The purpose of this article is to report the pattern and frequency of maxillofacial injuries resulting from all-terrain vehicle (ATV) accidents, to evaluate the mechanisms of injury, to document the length of hospital stay, and to characterize other associated injuries in patients presenting to a level 1 trauma center. Patients and Methods: The records of patients admitted to the University of Kentucky Medical Center from July 1, 1995 through August 1996 with an ATV-related injury were reviewed. Patients were included in the study if the events of their injury, demographic data, and the specifics of their perioperative care were sufficiently documented to provide the information pertinent to the investigation. Age, sex, mechanism of injury, facial injuries, associated injuries, and length of stay were the factors considered for the study. Results: Seventy-two patients met the criteria for the study. Fifty-nine (82%) were male, and 13 (18%) were female. Forty patients required operative intervention. Twenty-five (35%) had soft tissue or bony injuries to the m axillofacial region. One mandibular and 13 midface fractures were identified. Twelve of the patients with midface injuries had multiple facial fractures. Orbital floor fractures occurred in seven patients. Two patients required unilateral enucleation of the globe. Ten soft tissue injuries were diagnosed. Extremity fractures (n = 16) and closed head injuries (n = 17) were the most commonly associated injuries. The length of hospital stay for all the subjects identified in the study averaged 4.7 days. ATV rollover and being thrown from a moving ATV were the most common mechanisms of injury. Conclusions: Head and maxillofacial injuries, particularly midface injuries, are common findings after ATV accidents. Orbital trauma with serious globe injury was a striking feature of this study. Multiple systems injuries should always be anticipated and identified. The public should be alerted to the hazards of imprudent recreational vehicle use.

This study investigates the hypothesis that continuous administration of indomethacin (a cyclo-oxygenase inhibitor) will chronically reduce body temperature (TB) in burned rats (i.e., modulate "true" fever). Male Sprague-Dawley rats had radio transmitters and osmotic pumps (containing indomethacin) placed in the peritoneal cavity, and 7 days later large full-thickness scald burns were produced. Activity and TB were continually recorded through the 14th postburn day (PBD). There were 4 experimental groups: burn + indomethacin (B-In), n = 9; burn + polyethylene glycol (B-Peg), n = 6; control + indomethacin (C-In), n = 9; and control + polyethylene glycol (C-Peg), n = 6. From PBD 5 through PBD 10, the B-Peg group had consistently and significantly higher TB during light hours than the B-In, C-In, and C-Peg groups. From PBD 7 through PBD 12, the B-In group had an average TB during light hours significantly lower or not different than the C-In and C-Peg groups. These results support the hypothesis that in this burned-rat model chronically increased TB during the light hours may be "fever" (rather than hyperthermia) and that the final effector link could be a prostanoid because changes in activity do not explain the changes in body temperature.

The development of a more aggressive approach to burn wound management, leading to complete excision within 72 hours after burn, has led some to conclude that total early excision is a major force behind improved survival rates. We have summarized the results of treatment of 1507 patients with burn injuries treated between 1967 and 1986. Wounds were managed with use of standard topical therapy, occlusive dressings, and staged excision and grafting of full-thickness injury or deep dermal injury (not healed by 21 days). Data were analyzed with use of a logistic-regression model because, with the exception of older patient cohorts, the data did not fit the probit model. The major determinants predicting death were the percentage of body surface area burned, age 2 , smoke inhalation, and the percentage of full-thickness burn. Concordance was 97%. These data show that aggressive sequential wound excision and grafting produces end results comparable with those achieved with complete early burn wound excision for similar age ranges and injury. Early harvest of available donor sites in patients with large burns may be more important to survival than complete early wound excision.

In the medical community, the practice of admitting all electrical burns for 24–48 h of observation, monitoring and laboratory evaluation is widespread. This retrospective review of paediatric electrical burns was conducted to determine which patients may safely be treated as outpatients. Retrospective analysis of all paediatric burns admitted between 1980 and 1991 identified 35 patients with electrical injuries. Patients were divided into two groups for analysis: those burned by exposure to household voltages (120–240 V; n=26) and those exposed to high voltages, in excess of 1000 V (n=9). The majority of household electrical injuries occurred secondary to contact with the household 120 V (2126). Contact with an extremity accounted for the largest number of these injuries (1826). The mouth was the second most frequent site of injury (726). Most of these patients (2026) had < 1 per cent BSA burn. No patient in the household-voltage group had an arrythmia that required treatment, nor were there any identified examples of compartment syndrome or other vascular complications. Seven patients did require minimal skin grafting. No deaths occurred in either group. The patients in the household-voltage group were significantly younger. High-voltage electrical injuries occurred in an older patient population and required more aggressive care and surgical intervention. This was evident at the time of initial evaluation. Based on these data, healthy children with small partial-thickness electrical burns and no initial evidence of cardiac or neurovascular injury do not appear to need hospital admission.

Purpose The satisfaction-of-search (SOS) effect occurs when an abnormality on an image is missed because another is found. The aim of this experiment was to test whether severe distracting fractures control the magnitude of SOS on other fractures when both appear in a single CT image. Methods The institutional review board approved this study. The experimental (SOS) condition included 35 cervical spine CT cases, all of which contained severe cervical spine injuries. For each of these cases, a similar case was found that had no injuries. Image modification software was developed to add simulated fractures to each pair of cases, with and without a major injury. Sixteen different minor fractures were added to 16 of the 35 pairs of images. The 35 cases without native injuries constituted a control (non-SOS) condition mixed in a random order. Twenty radiologists read 35 mixed cases in each of two sessions. False-positive evaluations were collected only for cases without simulated fractures. Results An SOS effect on the detection of simulated fractures was not observed. There was a nonsignificant ( P = .07) finding of poorer detection in the presence of cases with severe injuries. However, the magnitude of the effect was no greater than has been observed for less severe distracting injuries. Conclusions The outcome agrees with the results of two previous experiments that failed to yield an SOS effect associated with detecting severe injuries, suggesting that the severity of a distracting injury does not determine whether a second injury is discovered.

This study in burned rats studied at two ambient temperatures (22 degrees and 28 degrees C) and housed at 28 degrees C was designed to investigate the role of catecholamines in the maintenance of thermal homeostasis following burn injury. Two weeks prior to burn or sham burn, animals underwent adrenal medullectomy or sham adrenal medullectomy. Between postburn days 9 and 13, simultaneous direct and indirect calorimetry was performed following administration of 2mg/kg of phentolamine (alpha adrenergic blocking agent) via a carotid arterial line. Following administration of phentolamine, heat production and body temperature decreased and heat loss increased immediately. The cooling slopes for the burn groups were significantly steeper than for the control groups, within ambient temperatures. Within ambient temperatures, the presence or absence of the adrenal medulla had no discernible effect on the cooling slope of the burns or the controls. The burned animals cooled 1.9-3.5 times faster at 22 degrees than at 28 degrees C, and controls cooled 2.0-3.9 times faster at 22 degrees than at 28 degrees C. Phentolamine produced a several-fold increase in serum concentrations of both norephinephrine (NE) and epinephrine (E), indicating a gross overlap in alpha and beta adrenergic receptor utilization for E and NE. The progressive cooling of the adrenal demedullated burn group at 22 degrees C following phentolamine administration seems to indicate that norepinephrine is calorigenic for rats under these experimental circumstances. These experimental results indicate a relatively non-essential role for catecholamines in the maintenance of thermal homeostasis within the thermal neutral zone in the rat.

This prospective randomized study was performed to evaluate the metabolic and thermal responsiveness of patients with burns to thermal stress with three protocols of wound care: group I (n = 7) treated with dressings and variable ambient temperature selected for patients subjective comfort; group II (n = 7) treated without dressings and variable ambient temperature for patient comfort; group III (n = 6) treated without dressings and ambient temperature of 25 degrees C, electromagnetic heaters were set to achieve patient subjective comfort; and group IV (n = 6) healthy volunteers. After baseline partitional calorimetry was performed, individual patients were cold-challenged while subjectively comfortable by sequentially lowering either the ambient temperature or the output from the electromagnetic heaters. Heat balance and temperatures were obtained after each perturbation in external energy support. For patients in groups I and II, subjective perception of thermal comfort (warm, neutral, neutral and fed, cool, or cold) was more strongly correlated (p < 0.02) with the changes in the rate of heat production than the actual ambient temperature. For patients treated with electromagnetic heaters, changes in heat production were most strongly correlated with the energy output from the electromagnetic heaters. Even though the environmental conditions required to achieve a particular level of comfort are quite different between treatment groups, the difference in temperature between the patient's surface and ambient is approximately the same for groups I, II, and IV for each subjective state.(ABSTRACT TRUNCATED AT 250 WORDS)

Burn injury in man is characterized by increased body temperature proportional to burn wound size and may represent fever and/or hyperthermia. A nonseptic animal model used to study this phenomena has not been described. To test the hypothesis that large burn injuries in rats would produce increased body temperature, the rectal, skin, and body temperatures were sequentially measured and were calculated for rats in the control group and rats with burn injuries covering 26% to 63% of the body surface area [or = 35%, 36% to 45%, andor = 46% body surface area]. The group with burns coveringor = 46% of the body surface area had significantly higher rectal temperatures than did at least one other group on postburn days 7, 9, 11, 13, 18, and 20. On postburn days 7 and 11 this increase was significantly higher than that of all burn and control groups. Animals did not demonstrate any overt evidence of wound infection. These data do not establish a cause for increased body temperature after burn injury but suggest that a reproducible animal model may be possible for the study of the cause of increased body temperature after burn injury.

We report heat balance studies and plasma catecholamine values for 49 children and young adults with healed burn wounds (age range 0.6 to 31 years and burn range 1% to 82% body surface area burned; mean 41%). All measurements were made during the week of discharge. Heat production for patients with healed burns was not significantly different from predicted normal values. However, compartmented heat loss demonstrated a persistent increment in evaporative heat loss that was secondary to continued elevation of cutaneous water vapor loss immediately after wound closure. A reciprocal decrement in dry heat loss was demonstrated (as a result of a cooler average surface temperature, 0.84 degree C cooler than the average integrated skin temperature of five normal volunteers who were studied in our unit under similar environmental conditions). Mean values for plasma catecholamines were in the normal range: epinephrine = 56 +/- 37 pg/ml, norepinephrine = 385 +/- 220 pg/ml, and dopamine = 34 +/- 29 pg/ml. In conclusion, patients with freshly healed burn wounds have normal rates of heat production; however, there is a residual increment in transcutaneous water vapor loss, which produces surface cooling and decreased average surface temperature, which in turn lowers dry heat loss by an approximately equivalent amount.

Rats with burn injuries demonstrate changes in thermoregulation including an upward shift of the set-point and reference temperatures with no change in sensitivity of the response in heat production to displacement of the temperature of the preoptic anterior hypothalamus. In the present studies, the response in plasma and urinary catecholamines to burn injury after destruction of the preoptic anterior hypothalamus was examined in the rat. Preoptic anterior hypothalamic lesioning impaired the hypermetabolic response to burn injury, and at 22 degrees C, burned lesioned rats were hypothermic. Furthermore, plasma levels and urinary excretion rates for catecholamines were not decreased in burned lesioned rats, but rather showed an inverse relationship with heat production. Burned lesioned rats were capable of maintaining body temperature at an ambient temperature of 28 degrees C. This suggests that a less precise thermoregulation is present in lesioned animals. Rats in which the preoptic anterior hypothalamus has been destroyed have reduced tolerance to burn injury.

The effect of early enteral feeding on the hypermetabolic response following burn injury in a rat burn model has been investigated. The rates of heat production and partitioned heat loss were determined on the fourteenth postburn day for five treatment groups: I) burn, fed rat chow ad libitum starting 2 hours postburn; II) burn, fed by gastrostomy beginning 2 hours postburn; III) burn, fed by gastrostomy, delayed until 72 hours postburn; IV) controls, fed by gastrostomy 2 hours post anesthesia; and V) controls, fed rat chow ad libitum 2 hours post anesthesia. Gastrostomy feedings delivered 175 kcal/kg.day. The mean rates of heat production and heat loss for the three burn groups did not differ significantly whether rats were fed chow ad libitum, or by gastrostomy early or late. Contrary to previous studies using a guinea pig model, method and timing of feeding in this burned rat model had no significant effect on the postburn increment in the rate of heat loss and the corresponding increment in the rate of heat production.

Hypermetabolism proportional to wound size is the expected response in patients who sustain large burns. This metabolic response persists until wound closure is achieved. The value of this response to the injured host remains unproven. Between 1978 and 1991, 104 patients with burns covering 30% or more of the body surface area underwent partitional calorimetry as a component of various research protocols. Thirteen of these patients failed to demonstrate an increase in metabolic rate as compared with a control group. These patients without hypermetabolism were compared with case-matched patients who demonstrated the expected increase in metabolic rate. Although they were not hypermetabolic in response to the burn injury, five of these patients were exposed to a cold stress and were able to increase their metabolic rate appropriately. The failure to mount a hypermetabolic response did not impact the clinical course as measured by survival, length of hospital stay, or maximum weight loss.

This study investigates the hypothesis that indomethacin's ability to prevent "fever" following burn injury in rats is mediated via decreased plasma concentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing indomethacin placed in the peritoneal cavity. Seven days later full thickness scald burns to 50% of the body surface area were produced. Following burn injuries, daily blood samples were obtained from a carotid catheter for assay of lipopolysaccharide (LPS), interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body temperature (T(B)) and activity index were obtained every five minutes by telemetry. There were four experimental groups: burn + indomethacin (B-In); burn + polyethylene glycol (Peg) (B-Peg); control + indomethacin (C-In); and control + Peg (C-Peg). Burned animals demonstrated a significant two-fold increase in plasma IL-1alpha levels (p=0.004) and a seven-fold increment in IL-6 (p=0.0001) through the 7th PBD, and indomethacin administration had no significant effect upon the cytokine plasma levels. There were no significant increases in IL-1beta, TNF-alpha or LPS in any group. Indomethacin eliminated the chronic increase in T(B) following burn injury, and this effect was not produced by changes in plasma levels of the endogenous pyrogens IL-1alpha and IL-6.

In previous studies, we established that circulating epinephrine (E) is not essential for a normal hypermetabolic response to burn injury in the rat, within the zone of thermal neutrality. In other studies, burned rats with adrenal medullectomy (AdxB) studied at 22 degrees C were unable to maintain rectal temperature (TR) after alpha-adrenergic blockage. These data suggest that norepinephrine (NE) is calorigenic in such animals without formal cold acclimation. These studies investigate the hypothesis that, contrary to the usual belief, norepinephrine might be calorigenic in rats without formal cold acclimation. Burned (B) and control (C) rats with adrenal medullectomies (Adx) and Sham (S) Adx (AdxB, SAdxB, AdxC, and SAdxC) were housed at either 22 degrees C or 28 degrees C. Calorimetry was performed during the eighth to eleventh days after the burn. For groups housed at 22 degrees C and studied at 28 degrees C, NE given intravenously (iv) produced an average 16.5%+/-3.3% increment in heat production (HP) for the four groups, which was significant for AdxB, SAdxB, and SAdxC. Intravenous administration of E produced an average increment in HP of 4.44%+/-4.1%, which was not significant. HP was significantly higher after NE than E in three cases. Studies with animals housed at 28 degrees C and studied at 28 degrees C produced intermediate but similar results. For groups housed at 28 degrees C and studied at 22 degrees C, iv administration of E and NE produced average decreases in He of 18%+/-6.7% for E and 10.75%+/-4.7% for NE. Except for the AdxC group, these differences were significant. These data suggest that chronic exposure to an ambient temperature of 22 degrees C produces an enhanced calorigenic response to NE in burn and control rats. Based on the data presented here, combined with earlier studies, NE must be considered as a facilitator for hypermetabolic response to burn injury in the rat. It is interesting to speculate whether NE is calorigenic for patients with large burn wounds, which are managed without dressings at ambient temperatures below thermal neutrality.

We investigated the possible causal relationship between interleukin-6 (IL-6) and increased body temperature (T(B)) in a rat burn model. Transmitters for measuring core temperature and estimating activity were implanted in the abdominal cavity. Animals in the burn group were clipped and received full-thickness scald burns to 45% to 55% of the body surface area, and control animals were clipped. T(B) and activity were measured continuously through the tenth postburn day. Carotid lines were placed, and serial blood samples obtained for lipopolysaccharide, IL-6, and tumor necrosis factor-alpha assay. From the third through the tenth postburn day, the burn group had a consistently significantly higher T(B) during light hours than the control group did (average, 0.45 degrees C +/- 10 degrees C, p = 0.0001). Differences in activity during light hours were not significant between the two groups, therefore, do not account for the observed significant difference in T(B). The average IL-6 serum levels were 3.5-fold higher for the burned animals. In this study, burn and control serum levels of IL-6 demonstrated positive correlation with T(B). These data suggest, but do not prove, a causal relationship between IL-6 and fever in the rat burn model, and make it unlikely that circulating systemic lipopolysaccharide is the cause.

Burn (B) and control (C) rats with and without adrenal medullectomy (Adx) 9-11 days postburn underwent warning and cooling of the preoptic anterior hypothalamus (POAH) during calorimetry at 22 degrees and 28 degrees C ambient. Blood was drawn for catecholamine assay during each displacement of the POAH temperature (Thy). The heat production (Hp) for the AdxB group at 22 degrees and 28 degrees C was not different from the Hp for the sham AdxB group (80 +/- 4 vs 86 +/- 8 at 22 degrees C, 58 +/- 8 vs 64 +/- 7 W/m2 at 28 degrees C) in spite of there being no detectable circulating epinephrine (E) for the AdxB groups. Cooling of the POAH of the AdxB 22 degrees C group, however, did not induce a further increment in Hp, in contrast to all other groups. Thy demonstrated good significant negative linear correlation with Hp for all groups. The resulting slopes were not significantly different from one another, indicating no difference in thermal sensitivity of the POAH between the groups. In four of eight groups plasma norepinephrine (NE) demonstrated positive correlation with Hp and in five of eight groups negative correlation with Thy, Plasma E values did not correlate with Hp and demonstrated negative correlation with Thy in two of four possible groups. These data show that postburn hypermetabolism is not dependent on E in the rat and suggest that NE may be calorigenic in burned rats.

Rats, with the preoptic anterior hypothalamus implanted with two thermodes and a thermocouple reentry tube, had simultaneous direct and indirect calorimetry performed [during the ninth to eleventh postburn day interval] at ambient temperatures of 22 degrees and 28 degrees C. During calorimetry, blood was drawn at baseline and near the end of each period of displacement of the preoptic anterior hypothalamus temperature for catecholamine assay. Cooling the preoptic anterior hypothalamus resulted in a significant increase in heat production and plasma epinephrine and norepinephrine concentrations for both burn and control groups at 22 degrees C and 28 degrees C (p < 0.05 for all comparisons). Heat production demonstrated consistent negative linear correlation with preoptic anterior hypothalamic temperature. Plasma epinephrine values correlated with preoptic anterior hypothalamic temperature for only the controls at 28 degrees C ambient, whereas norepinephrine had significant linear correlation with heat production for all groups and significant negative linear correlation with preoptic anterior hypothalamic temperature. These data indicate norepinephrine may be more important than epinephrine in the maintenance of postburn hypermetabolism in this rat burn model while demonstrating that the hypermetabolism is appropriately responsive to perturbation of preoptic anterior hypothalamic temperature.

Metabolic and temperature data were collected for 56 patients with burns managed with four wound care protocols. Group I (n = 7) treated with dressings and variable ambient temperature selected for patient subjective comfort; group II (n = 7) managed without dressings and variable ambient temperature for patient comfort; group III (n = 6) no dressings, ambient temperature of 25 degrees C and the output of electromagnetic heaters adjusted for patient comfort; group IV (n = 36) dressings and ambient temperature of 28 degrees C. All groups were cold challenged: groups I and II by sequentially lowering ambient temperature, group III by decreasing the electromagnetic heater output, and group IV by removing dressings with ambient temperature remaining at 28 degrees C. Only groups II and IV demonstrated correlation between percent body surface area burn and heat production. The slope of the regression for group IV neutral was significantly less than that for group IV cold and group II neutral and cold. The relationship between percent body surface area burn and rectal temperature for groups I, II, and III neutral was equal to .03 degrees C increase in rectal temperature per 1% body surface area burn (Y = 37 + 0.03; r = 0.74; df 18; p < 0.01) and was not significantly different when cold. This predicts a 1.5 degrees C increase in rectal temperature for a patient with a 50% body surface area burn who does not have sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was conducted to examine the guinea pig as a suitable model for the study of the postburn hypermetabolic response and the febrile response that accompanies burn injury in man. Thirty animals were randomly assigned to four groups:50% body surface area burn (n = 6); 45% to 50% body surface area burn (n = 10);45% body surface area burn (n = 6); and controls (n = 8). On postburn days 3, 7, 11, 13, and 15, sequential temperature measurements were made. On postburn days 7 to 15, the randomly selected burn group (n = 12) and the control group (n = 8) had calorimetry studies performed. Sequential rectal temperature data demonstrate that the guinea pig does not mount a prolonged or consistent febrile response after burn injury (p0.05 for burn group vs control group on postburn days 7 to 13; p0.05 for postburn days 3 and 15 only). However, the burned guinea pig is significantly hypermetabolic after burn injury, with significant increases in dry and evaporative heat loss. The hypermetabolic response was proportional to burn wound size. Guinea pigs are not an ideal model for the study of the postburn febrile response; however, this is an excellent model for the study of postburn hypermetabolism.

Ibuprofen is an effective antipyretic in the postburn period and produces associated decrements in the hypermetabolic response. Burn injury is capable of altering the kinetics of many drugs, making the predictable use of agents such as ibuprofen difficult. Ten patients with serious burns were studied after the administration of 10 mg/kg ibuprofen suspension. The half-life varied from 1.4 to 5.1 hours, depending on the site of administration and/or the presence of solid food. The reported half-life for ibuprofen suspension is 1.8 to 2 hours. Burn size did not alter ibuprofen half-life or area under the time-concentration curve. Maximum ibuprofen concentration varied greatly, depending on route of administration. Time to maximal temperature reduction was between 2 and 3 hours after drug administration. Although the precise level of ibuprofen needed for cyclooxygenase inhibition is unknown, enteral administration results in levels below the targeted 10 to 20 mcg/ml for much of the traditional 6-hour dosing interval. Future studies with ibuprofen in the burn population must standardize more than just total dose.

This study was performed to establish the relative efficiency of occlusive dressings and variable ambient temperature (group I) versus no dressings and variable ambient temperature (group II) versus no dressings and electromagnetic heaters (group III) for controlling the postburn hypermetabolic response. Fifteen burn patients and five normal controls (group IV) were studied when subjectively comfortable using partitional calorimetry, after which each patient was cold stressed by sequentially decreasing external energy support, and repeating calorimetry studies and serial plasma catecholamine assays. The percentage increase in heat production above predicted normal values was significantly increased for all groups when cold (C) versus neutral (N) (group I: [N] 24 +/- 24 versus [C] 49 +/- 25%; group II: [N] 46 +/- 35 versus [C] 74 +/- 47%; group III: [N] 21 +/- 20 versus [C] 78 +/- 25%; group IV: [N] -9 +/- 12 versus [C] 16 +/- 10%, p less than 0.05 all comparisons). Plasma catecholamine values did not increase significantly when patients were subjectively cold. These studies do not support the role of catecholamines as the primary mediator in the cause of the postburn hypermetabolic response. Using the patients' subjective comfort status as a guide for external energy support, it is possible to greatly reduce but not to eliminate the hypermetabolic response to burn injury.

A group of 15 burned children and young adults with large burns (mean, 41% +/- 15% BSA) were administered ibuprofen (40 mg/kg for 3 days). Each patient served as his or her own control in this crossover study (with and without ibuprofen). Paired calorimetric and temperature studies and urinary nitrogen measurements were performed. No nitrogen-sparing effect was identified for this dose of ibuprofen. However, patients demonstrated a statistically significant reduction in average rectal temperature (0.67 degrees C decreases) (p less than 0.01) and in metabolic rate (11.4% decreases) (p less than 0.01) while taking ibuprofen. Linear regression analysis of the reduction in temperature versus the reduction in metabolic rate yielded a statistically significant correlation (p less than 0.01) with a slope of 13.6% reduction in metabolic rate per degree centigrade reduction in the 72-hour average rectal temperature. These results support the hypothesis that ibuprofen attenuates the hypermetabolic response to thermal injury by blunting the temperature elevation that is usually seen.

Metabolic studies were performed on 23 burned children. They were studied sequentially until their burn wounds were healed. A metabolic study lasted 20 minutes, during which continuous measurements were made of O2 consumption and CO2 production rates, rectal temperature, average surface temperatures (dressings, skin and wound), body heat content, and rate of body weight loss using a bed scale. These measurements allowed solution of the heat balance equation for each study period. After 24 hours in a constant temperature room kept at 28 C and 40% relative humidity, metabolic studies were initiated when blood was drawn for catecholamine assay, followed by a metabolic analysis, after which dressings were removed and fresh silvadene applied to the wounds. No dressings were applied. Metabolic analyses were repeated after two and four hours of exposure, after which blood for catecholamine analysis was drawn and the study terminated. Without dressings in a thermally neutral environment, burn patients demonstrated an increased rate of heat loss of 27 watts/square meter body surface area (W/M2), compared with the predicted normal. The major portion of this increment is by evaporation, which increased 300%. The rate of heat production equals heat loss, and is increased 50% above the predicted normal. Occlusive dressings result in a 15 W/M2 decrease in the rate of heat loss, about evenly divided between evaporative and dry routes, with a corresponding 15 W/M2 decrease in the rate of heat production. Plasma catecholamine levels of bandaged burn patients are not significantly different from values for healed burn patients, and do not correlate with the rate of heat production. The increased heat production of burn patients is a response to an increased rate of heat loss, not vice versa. The use of occlusive dressings substantially reduces the energy requirements to manageable levels, even in patients with very large burns.

The preoptic anterior hypothalamus (POAH) of rats housed at three ambient temperatures was implanted with perfusion apparatuses. Response of heat production to displacement of POAH temperature was determined for control animals and animals with burns (31% +/- 3% total body surface area). At an ambient temperature of 22 degrees C there was a significant increase in thermosensitivity of the POAH for both control rats and rats with burns compared with thermosensitivity at 32 degrees C. Within ambient temperatures there was no effect on thermosensitivity detected for rats with burns compared with control rats. The threshold temperature for heat production was shifted significantly upward (p less than 0.05) both by a lower ambient temperature and by burn injury. The reference temperature for heat production was also shifted to the right by burn injury (p less than 0.05). The significant shifts to the right for threshold temperature and reference temperature for heat production enhance the organisms's ability to meet the stress of the hypermetabolic response. At a warm ambient temperature (32 degrees C) there are no significant differences in thermoregulation detected in animals with burns or control animals.

A low cardiac output state is observed following major thermal injury in both experimental and clinical settings. The major determinants of cardiac output are preload, afterload, and the contractile state of the myocardium. The effects of afterload reduction in acute thermal injury are the focus of this experiment. Pure-bred young nonpregnant ewes of the Suffolk strain were utilized to determine the effect of afterload reduction on the cardiac index in experimental burn shock. Four groups of animals were studied; Group 1: unburned control (n = 5); Group 2: unburned-treated with sodium nitroprusside (n = 5); Group 3: 40% burned (n = 9); and Group 4: 40% burned-treated with sodium nitroprusside (n = 9). Pulmonary arterial, intravenous, and bladder catheters were placed in all animals. Following anesthesia with or without a burn, the animals were monitored for 24 hours. Measured and calculated parameters included cardiac index, pulmonary arterial and arterial pressures, pulmonary and systemic vascular resistance indices, shunt, arterial and mixed venous blood gases and pH, and hematocrit. When burned animals with and without nitroprusside were compared, significantly higher cardiac indices, expressed as per cent of baseline, were noted for the sodium nitroprusside-treated group at 8 and 12 hours postburn. The burned-treated animals' cardiac index was not significantly different from control animals' at 8 hours postburn. However, the burned-untreated animals had significantly depressed cardiac indices until 18 hours postburn.(ABSTRACT TRUNCATED AT 250 WORDS)

This review was undertaken to elucidate the trends in copper, zinc, total serum protein, and ceruloplasmin levels in patients with thermal trauma. Medical records of pediatric and adult patients were retrospectively reviewed. The findings showed a significant linear decline in mean plasma copper, ceruloplasmin, and total serum protein during the first three days postburn, followed in general by a gradual rise in levels; however, patients with burns larger than 60% TBSA maintained copper, zinc, and ceruloplasmin levels significantly below the lower limits of normal during the observation period. Significant decrements in copper, zinc, total serum protein, and ceruloplasmin levels have been demonstrated in these patients. Trace metal determinations should be obtained in patients with significant burns soon after admission and routinely throughout their hospital course. Specific trace metal supplementation should be administered when indicated.

Pharmacological doses of cimetidine have been reported to reduce oedema formation in murine burn models. Sprague-Dawley rats subjected to a 30 per cent full-thickness burn were treated with cimetidine (200 mg/kg) pre and post burn. Untreated, burned animals and sham-burned animals were also studied. No beneficial effects of cimetidine were demonstrated. Cimitidine increased the water content in lung, stomach and eschar of burned animals. No differences were seen in serum or urine electrolytes, or extrarenal water loss. Cimetidine did reduce serum hyperosmolality seen in unresuscitated burned animals. Multiple doses of cimetidine following thermal injury were associated with a significant increment in mortality rate.

The liberal use of the colostomy, beginning in World War II, was the greatest single factor in reducing the mortality of colon and rectal injuries [I]. From such experience, temporary colostomy has become an essential part of the treatment of many emergent and some elective colon conditions. Thus, colostomy closure is now a common procedure. Despite this universal adoption and the seemingly low risk of the procedure, colostomy closure results in a significant morbidity (10 to 50 per cent) and occasional mortality (0.5 to 1 per cent). Initially, problems associated with colostomies and their closure were accepted as a matter of course. Recently, the surgical literature has included recommendations designed to reduce the morbidity of colostomy closure. Some authors have suggested that colostomy be avoided under certain conditions when it would normally be done [z]. To identify factors that contribute to the high morbidity of colostomy closure, a retrospective study of our experience was performed. Specific aims of the study included: (1) identification of problems related to colostomy closure; (2) correlation of complications with factors related to the colostomy and its management; and (3) formulation of an approach to the handling of colostomy closure.

Unanesthetized male Sprague-Dawley rats were bled 40% of their blood volume. After 1 hour of hypovolemia, the animals were resuscitated with either lactated Ringer's solution (LRS) or hypertonic lactated saline (HLS). They received a volume of crystalloid equal to the shed blood volume or twice the shed blood volume. Twenty-four hours after resuscitation, the animals were sacrificed and the brains excised. The per cent water content was determined. Severe hemorrhage without resuscitation resulted in significantly increased intracerebral water content (77.7 +/- 1.0 vs 78.9 +/- 0.7 p less than 0.05). Resuscitation with twice the shed blood volume of either LRS or HLS prevented this increase in intracerebral water. These data support the conclusion that adequate resuscitation is the critical factor in preventing cerebral edema following acute severe hemorrhage.

Previous studies have indicated that combining cerium nitrate with silver sulfadiazine (Silvadene, Marion Labs) yields a superior topical agent for the treatment of burns. Cerium nitrate in silver sulfadiazine was tested in a controlled study with silver sulfadiazine alone. The study population consisted of two groups of children suffering burns greater than 30% of the body surface. The patients ranged in size from 1 to 21 years. The study period was for the first 10 weeks of hospitalization. Quantitative surface cultures were used to monitor burn wound flora. No superiority for the silver sulfadiazine-cerium nitrate combination was demonstrated. In fact, cultures indicate a significantly greater percentage of Gram-negative pathogens in patients treated with the cerium mixture. Cerium nitrate could possibly prove of greatest benefit if used as a reserve therapy for colonizing organisms which do not routinely respond to silver sulfadiazine.