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Biomedical subjects

S K Szyfelbein

Publications and source records attributed to S K Szyfelbein.

At least 19 recordsLinked to original sources

Trends in blood conservation in burn care.

Traditional burn surgery is very bloody, but wide use of blood conserving strategies is becoming common. Uniform application of blood conserving techniques of burn wound excision may substantially decrease blood utilization in burn patients. We chose to examine this trend in our unit. All fresh frozen plasma (FFP) and packed red blood cell (pRBC) use in children with burns of 10% or more of the body surface who were admitted during 2-3 year intervals, separated by a decade, was reviewed in detail. Three subgroups were separately analyzed: children with 10-24% (small), 25-49% (medium) and 50-100% (large) body surface area burns. Between these two intervals a major emphasis was made in techniques of blood conservation during surgery and fresh frozen plasma was replaced by 5% albumin as the routine resuscitative colloid. In Group 1, there were 189 children, of whom 184 (97%) survived to discharge. In Group 2, there were 203 children, of whom 199 (98%) survived to discharge (N.S.). All subgroups were well matched for age, weight and burn size. Discharge hemocrits exceeded 30% in all subgroups. Reductions in FFP use were 100, 95 and 97% in the small, medium and large burn size groups, respectively. Reductions in pRBC use were 89, 63, and 80% in the small, medium and large burn size groups, respectively. These differences were all highly significant (P<0.001). Uniform application of blood conserving techniques of burn wound excision result in highly significant reductions in blood product exposure without sacrifice of clinical outcomes.

Albumins↗

Neuromuscular effects of mivacurium in 2- to 12-yr-old children with burn injury.

BACKGROUND: Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium. METHODS: Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion. RESULTS: The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn. CONCLUSIONS: A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.)

Body Weight↗

Staged high-dose epinephrine clysis is safe and effective in extensive tangential burn excisions in children.

Prodigious blood loss commonly accompanies extensive tangential burn excisions. Staged high-dose epinephrine clysis may facilitate blood conserving excisional burn surgery. Prospective data was collected in 25 consecutive children who underwent tangential excision over the torso of at least 10% of the body surface with staged high dose epinephrine clysis. The children had an average age of 6.3 +/- 1.1 years and burn size of 45.7 +/- 3.9%. Total operative wound size (excision plus donor site) averaged 2 +/- 0.8% of the body surface. Total dose of epinephrine averaged 24.6 +/- 2.8 mcg/kg. Based on pre- and postoperative hematocrit and known volume of transfusion, the percent of the total blood volume lost per percent total wound generated averaged 0.98 +/- 0.19% of the blood volume per % of the body surface; 18 of the children (72%) required no blood in the perioperative period. There were no complications related to epinephrine use, graft take averaged 98 +/- 0.6% and all children survived and have been discharged home in good condition. Due to its rapid metabolism, subcutaneous epinephrine at high doses can be repetitively administered as long as time is allowed for its metabolism to occur. Use of this technique facilitates a marked reduction in blood requirements for these traditionally bloody operations.

Adolescent↗

Intraoperative reflectance oximetry in burn patients.

OBJECTIVE: Transmission oximetry sites for intraoperative monitoring are frequently difficult to find in burn patients, as standard transmission oximetry sites are often burned or contained within the operative field. The objective of this study was to determine if reflectance oximetry is of potential value in monitoring this group of patients. METHODS: A total of 16 operative procedures in a group of acutely burned adult and pediatric patients with an average age of 9.7 years (range, 10 months to 37 years), average burn size of 42% of the body surface (range, 15% to 94%), and average weight of 34.2 kg (range, 9 to 100 kg) were done with simultaneous transmission and reflectance oximetry monitoring. RESULTS: During these 16 procedures in a diverse group of acutely burned adult and pediatric patients, there was no significant difference in saturations derived from transmission and reflectance oximetry probes. In smaller children, adequate signal for reflectance probe monitoring was often detected in hyperemic sites, such as healed partial thickness burn. CONCLUSIONS: This is the first published report documenting both the clinical use of the reflectance oximetry in burn patients and the clinical use of the Nellcor Oxisensor II RS-10 reflectance oximetry probe (Nellcor Corporation, Hayward, CA). This technique can facilitate the intraoperative monitoring of acutely burned adult and pediatric patients in whom standard transmission oximetry sites are difficult to find.

Adult↗

Spinal co-administration of peptide substance P antagonist increases antinociceptive effect of the opioid peptide biphalin.

Intrathecal injection of 0.25 micrograms of undecapeptide substance P antagonist (SPA) produced transient antinociception with a peak effect at 5 min. Increasing the SPA dose resulted in neurotoxicity. Intrathecal injection of the opioid peptide biphalin (BIP) produced antinociception for over 3 hrs without neurotoxicity. Co-administration of SPA (at subtoxic doses) increased BIP's antinociceptive effect. Naltrexone reversed analgesia due to BIP alone as well as after BIP+SPA.

Analgesics↗

Enhanced potency of intravenous, but not intrathecal, morphine and morphine-6-glucuronide after burn trauma.

We examined the analgesic effect of morphine (M) and its metabolite morphine-6-glucuronide (M6G) in a rat model of acute thermal trauma. M or M6G were given by intrathecal (IT) or intravenous (i.v.) routes after brief burn or sham burn delivered during inhalational anesthesia. In the sham group, M6G was significantly less potent than M when given i.v., yet tended to be more potent than M when given IT. For both drugs, thermal injury increased i.v. potency, yet decreased (for M) or displayed a trend to decrease (for M6G) It potency. The increased potency seen with i.v. but not IT opioid administration may reflect pharmacokinetic (e.g., diminished clearance) and/or pharmacodynamic responses (e.g., activation of peripheral opioid receptors) after thermal injury.

Analgesia↗

Morphine-3-glucuronide: silent regulator of morphine actions.

To assess whether stoichiometric manipulation of morphine (M) metabolism can enhance analgesia or slow the development of M tolerance we co-administered M-3- glucuronide (M3G) during single or repeated doses of morphine in rats. Although M3G itself lacked analgesic activity, co-injection of M3G with M increased and prolonged analgesia beyond that seen with M. In addition, diminution of the acute analgesic effect of M after 3 once-daily doses of M did not occur after daily co-injection of M3G and M. Thus the traditional view that tolerance to the effects of M is due solely to effects mediated through opioid receptors must be broadened to include the contributions of enzyme induction or stoichiometric equilibration of M3G in this process.

Analgesia↗

Tongue oximetry in children with extensive thermal injury: comparison with peripheral oximetry.

We undertook a prospective study of standard peripheral pulse oximetry versus a modified pulse oximeter probe applied to the tongue in order to determine the efficacy of this alternative monitoring site in children with thermal injuries. Ten patients with a mean age (+/- SD) of 7.5 +/- 4.5 yr were studied on 15 occasions. The mean weight (+/- SD) was 31.4 +/- 13.7 kg and percent surface area burn (+/- SD) was 56 +/- 21%. A total of 1,992 min of anaesthesia time was monitored. Both sites functioned simultaneously 47% of the time; the lingual but not the peripheral site functioned 28% of the time and only the peripheral site and not the lingual functioned 22% of the time. Neither site functioned 3% of the time. The tongue oximeter provided 563 min more monitoring time than the peripheral sites. The tongue oximeter also functioned in children with peripheral vasoconstriction when the peripheral sensor failed and was less susceptible to electrocautery interference. The tongue oximeter is a reasonable adjunct but not a substitute for peripheral oximetry since its application is limited to paralyzed, intubated patients.

Adolescent↗

Analgesic activity of a novel bivalent opioid peptide compared to morphine via different routes of administration.

A novel bivalent opioid tetrapeptide, biphalin (Tyr-D-Ala-Gly-Phe-NH)2, was synthesized based on structure-activity relationships. The analgesic activity of biphalin was assessed in comparison to morphine in rats. Drugs were administered subcutaneously (s.c.), intravenously (i.v.) and intrathecally (i.t.). Tail flick and tail pinch were used as tests for analgesia. Biphalin s.c. showed negligible analgesic activity, but when given i.v. produced significant analgesia, although less potent than morphine via this route. In contrast, intrathecal biphalin was more potent than morphine. These results indicate that biphalin has intrinsic activity that is compromised by enzymatic degradation or redistribution in the periphery, properties that may render it useful in exploring analgesic actions of locally applied opioids in the periphery without the likelihood of unwanted central effects.

Amino Acid Sequence↗

Enhanced potency of receptor-selective opioids after acute burn injury.

Dose-response curves of three receptor-selective opioids were established in a group of nonburned and a group of burned rats. Morphine (mu-agonist), biphalin (mu- and delta-agonist), and U50488H (kappa-agonist) were administered to each group, and analgesia was measured by tail flick latency testing. Each opioid had a significant increase in potency (i.e., a decrease in ED50 values) in the burned (15% body surface area) compared with the nonburned groups. Moderate doses of each drug (i.e., ED50 doses estimated from nonburned group data) in each case augmented stress-induced analgesia in the burned group. Analgesic doses failed to prevent a significant increase in plasma beta-endorphin and corticosterone after larger surface area (25%) burns. Regardless of receptor specificity, opioid analgesic potency is increased acutely after burn injuries.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Antinociception in the rat induced by a cold environment.

Rats placed in a cold environment (4 degrees C) for 2 h had a sustained increase in tail flick latency (TFL) as well as an increase in tail pinch latency (TPch) that was often biphasic with an early peak response at 15 min and a later, often higher, peak at 2 h. Plasma beta-endorphin levels after a modest increase at 5 min (24%) declined throughout the remaining time in the cold. The long-acting opioid antagonist naltrexone had no effect on TFL increases but led to greater increases in TPch (P less than 0.04). In morphine-tolerant rats TFL response was the same as in controls but TPch increases were greater (P less than 0.04). Rats exposed to 2 h of cold for 17 or 18 consecutive days generally developed tolerance to the analgesia of cold, i.e. TFL and TPch increases were diminished; however, the response to morphine on day 18 was the same as in rats never exposed to cold. Adrenalectomy and hypophysectomy led to significantly smaller increases in TFL (P less than 0.02 and P less than 0.001, respectively). The TPch response in contrast, was greater in adrenalectomized (P less than 0.001) and the same in hypophysectomized rats compared to sham controls. An opioid kappa receptor antagonist (Mr 1452) given prior to cold reduced both TFL and TPch response during the first hour. Thus the analgesia induced by cold appeared to shift from an early possibly kappa opioid to a later non-opioid form. The TFL effects seemed to be under hormonal influence while the TPch were not.

Adrenal Glands↗

Management of burn pain in children.

In spite of the many possible methods of pain control in the burned child satisfactory pain management may still be a problem, at times formidable. The most fruitful approach would seem to be frequent assessment of pain in the individual patient with a readiness to try alternative or additional measures when relief seems inadequate. In this way the most effective analgesic agent(s), route(s), and frequency of administration, as well as nonpharmacologic methods, can be determined for each child. Among those able to speak, pain estimation is usually easily accomplished. In infants and those intubated for supported ventilation, however, the task is more difficult. Nevertheless, careful observation of physiologic signs such as heart rate and blood pressure, facial expressions, body movement and position, and the quality of an infant's cries may in sum be sufficient to evaluate the intensity of pain. Monitoring of analgesic plasma levels to ascertain that they are within the ranges established for good analgesia and even determination of beta-endorphin blood levels may also aid in judging the adequacy of analgesia. By tailoring pain management methods to the needs of each child it may be possible to keep pain at acceptable levels in victims of burn injury.

Analgesics↗

Pituitary-adrenal stress response in the absence of brain-pituitary connections.

To examine whether an acute pituitary-adrenal response to stress may occur in vivo in the absence of hypothalamic-pituitary connections, we measured plasma beta-endorphin (beta-EP) and corticosterone (C) in rats after acute thermal injury. beta-EP rose significantly after thermal injury in normal rats and rats bearing pituitary-to-kidney autotransplants but not in animals with pituitary aspiration without reimplantation. Corticosterone responses paralleled beta-EP but were significant only in normal controls. Propranolol pretreatment did not reduce postburn beta-EP and C rises in autotransplanted animals. Therefore, since circulating factors contribute in vivo to pituitary-adrenal responses, the widespread practice of using "stress hormone" responses to quantitate perioperative stress or pain may in some circumstances be flawed.

Animals↗

Increases in plasma beta-endorphin and tail flick latency in the rat following burn injury.

In children with burn injuries we found, in earlier studies, an inverse association of plasma beta-endorphin immunoactivity (iB-EP) and pain levels. To further explore the effects of burn trauma on the peripheral release of beta-endorphin and the occurrence of centrally mediated stress analgesia, plasma iB-EP levels and tail flick latency (TFL) were measured in rats subjected (while anesthetized) to scald injury. In comparison to sham burn (dip in tepid water), burn injury increased plasma iB-EP and TFL; both the duration and magnitude of these effects were directly proportional to the extent of burns. In rats receiving no treatment, TFLs were unchanged throughout the time of the burn experiments. At 2 days post-burn TFLs were invariably back to pre-burn levels. Administration of the long-acting opioid antagonist naltrexone prior to burn injury prevented the rise in TFL. Thus the trauma of burns appeared to bring about a stress-induced analgesia (SIA). The marked increase in iB-EP during this SIA and its antagonism by naltrexone suggest that it was opioid and hormonal in character.

Analgesia↗

Intraoperative events diagnosed by expired carbon dioxide monitoring in children.

Expired carbon dioxide measurements (PeCO2) were used (1) to assess the adequacy of initial alveolar ventilation, and (2) to document intraoperative airway events and metabolic trends. Three hundred and thirty-one children were studied. Thirty-five intraoperative events were diagnosed by continuous PeCO2 monitoring; 20 were potentially life-threatening problems (malignant hyperthermia, circuit disconnection or leak, equipment failure, accidental extubation, endobronchial intubation, or kinked tube); only two of these were also diagnosed clinically. The duration of anaesthesia may be a factor: 3.9 hours for cases with events vs. 2.5 hours for cases without events (p less than 0.002). There was a higher incidence of hypercarbia (peak expired PeCO2 greater than or equal to 50) in children who were not intubated (29 per cent) compared to those who had an endotracheal tube in place (12 per cent) (p = 0.0001). Hypocarbia (peak expired PeCO2 less than or equal to 30) was more frequent in intubated cases (11 per cent) than in unintubated cases (three per cent) (p = 0.03). There was a high incidence of hypocarbia in infants less than one year of age (p = 0.02). We conclude: (1) life-threatening airway problems are common during anaesthesia in paediatric patients; (2) quantitative measurement of PeCO2 provides an early warning of potentially catastrophic anaesthetic mishaps; (3) the incidence of events increases with duration of anaesthesia.

Anesthesia↗

Cardiovascular and neuromuscular responses to high-dose pancuronium-metocurine in pediatric burned and reconstructive patients.

The efficacy of the combined use of pancuronium and metocurine (Pm-MTC) in high doses to produce rapid-onset muscle paralysis was evaluated in 15 patients with acute burns and 18 recovered burned patients scheduled for reconstructive surgery. Two and three times the previously determined ED95 of the combination for each group was used. (ED95 for Pm-MTC combination is 0.032/0.129 mg/kg for acute burns and 0.013/0.051 mg/kg for reconstructive patients.) Doubling ED95 produced 95% paralysis in 3.1 +/- 0.9 min in acutely burned children and in 4.3 +/- 0.7 min in reconstructive children (mean +/- SEM). These onset times were not significantly different from each other. Tripling the ED95 of the combination in burned children reduced the onset time to 1.3 +/- 0.14 min, but this was not significantly different from 2 X ED95 onset time in burned patients. The administration of 3 X ED95 to the reconstructive group, however, resulted in a significantly more rapid onset time of 1.8 +/- 0.4 min compared with 2 X ED95 in the same population. With 3 X ED95 the onset times between burn and reconstructive patients were not significantly different. Time for recovery of twitch to 25% of control twitch height (75% twitch depression) was significantly prolonged in burned patients compared with reconstructive patients for equipotent doses administered. Although the occasional patient showed prominent changes in heart rate and blood pressure, overall cardiovascular stability was impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

The assessment of pain and plasma beta-endorphin immunoactivity in burned children.

The need for better analgesia during burn dressing changes (BDCs) in acutely burned children led us to assess pain during BDC with a large 0-10 thermometer-like scale which was well accepted and appeared to reflect the varying degrees of pain that patients experienced. Pain scores were obtained at least once each minute throughout 33 BDCs in 15 patients of 8-17 years. Plasma levels of beta-endorphin immunoactivity (iB-EP) were measured at 5 intervals before and after BDC; mean values (+/- S.E.M.) ranged from 30.5 +/- 4.63 pg/ml (before BDC and analgesic) to 19.2 +/- 3.02 pg/ml (immediately following BDC). The mean pain score (MPS) for each BDC was inversely related to the iB-EP levels of that day (P less than 0.001 with 4 of the 5 iB-EP determinations). The MPS varied directly with the extent of burn injury and inversely with weight; the 2 variables together predicted MPS as well as the iB-EP alone (r2 = 43 and 36% respectively).

Administration, Topical↗