Stanislaw K. Szyfelbein

The assessment of pain and plasma β-endorphin immunoactivity in burned children☆

&NA; 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 &bgr;‐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 < 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).

Immunosuppression and temporary skin transplantation in the treatment of massive third degree burns.

A method of burn treatment (immunosuppression and temporary skin transplantation) for patients suffering from massive third degree burns is evaluated. The method is based on the prompt excision of all dead tissue (burn eschar) and immediate closure of the wound by skin grafts. Total wound closure is achieved before bacterial infection or organ failure takes place by carrying out all initial excision and grafting procedures within the first ten days post burn and supplementing the limited amount of autograft with allograft. Continuous wound closure is maintained for up to 50 days through immunosuppression. Both azathioprine and ATG have been used but ATG is preferred. During the period of immunosuppression, allograft is stepwise excised and replaced with autograft as autograft donor sites regenerate for recropping. Bacterial complications are minimized by housing the patient in the protected environment of the Bacteria Controlled Nursing Unit. Intensive protein and calorie alimentation are provided, and 0.5% aqueous AgNOa dressings are used. A swinging febrile illness has been associated with large areas of allograft rejection. Eleven children have been treated and seven have been returned to normal, productive schooling.

Right ventricular dysfunction in acute thermal injury

The elevated cardiac output (CO) and pulmonary artery hypertension (PAH) observed in thermal injury offers a unique opportunity to study the effects of a combined pressure-flow load on the right ventricle in previously healthy persons. Potential responses include a diminished right ventricular ejection fraction (RVEF), increased right ventricular end-diastolic volume index (RVEDVI), and augmented myocardial oxygen consumption because of increased systolic wall tension. We investigated these factors in 15 nonhypoxic patients without sepsis having 15–75% body surface area burns using flow directed catheters and the thermodilution technique. All patients increased their CO in response in fluid resuscitation, but six patients with an elevated mean pulmonary artery pressure (>20 mmHg) and increased pulmonary vascular resistance (>1.2 mmHg/min/L) had right ventricular dysfunction as evidenced by an increase (188 ± 15 ml/M-) in RVEDVI and a decreased (0.26 ± 4 ml/M2) RVEF. Patients without PAH had a smaller RVEDVI (115 ± 4 ml/M2) and larger RVEF (0.39 ± 0.02). Patients with PAH and RV dysfunction were older, had larger body surface area burns, lower systemic diàstolic artery pressures (63 ± 4 mmHg) and higher heart rates (114 ± 7 beats/min); RV end-diastolic pressures were minimally elevated (9.5 ± 1.4 mmHg). The decrease in RVEF and increase in RVEDVI may limit the hemodynamic response to fluid volume replacement and survival.

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 < 0.002). There was a higher incidence of hypercarbia (peak expired PeCO2≥ 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≤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) lifethreatening 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.RésuméL’6tude du CO2 en fin dexpiration (PeCO2) a été utilisée afin d’évaluer (1) la fonction respiratoire initiate et (2) pour documenter les événemenls per-opératoires touchant les voies aériennes ainsi que les changements métaboliques. 331 enfants ont été étudiés. 35 événements per-opératoires ont été diagnostiqués par une surveillance constante de la PeCO2; 20 représentaient des problèmes mettant en danger la vie (hyperthermie maligne, disconnection de circuit, fuite, bris d’équipement, extubation accidentelle, intubation endobronchique, ou tube endotrachéal coudd); seulement deux de ces événements ont été aussi diagnostiqués cliniquement. La durée de l’anesthésie pouvait aussi être un facteur: les présentants les accidents ont duré en moyenne 3.9 heurs contre 2.5 heures pour les cas n’ayant pas présenté de problèmes (p < 0.002). Il y avait un incidence plus élevée d’hypercarbie (PECO2 ≥ 50,) chez les enfants qui n’étaient pas intubés (29 pour cent) a comparé à ceux dont le tube endotrachéal élail en place (12 pour cent) (p = 0.0001). L’hypocarbie (PeCO2 ≤ 30) était plus fréquente chez les patients intubés (11 pour cent) que chez ceux qui n’étaient pas intubés (trois pour cent) (p = 0.03). It y avait une incidence plus grande d’hypocarbie chez les enfants âgés de moins qu’un an (p = 0.02). On colclut: 1) les problemes de voies aeriennes pouvant mettre en danger la vie sont fréquents lors de I’anesthésie pédiatrique; 2) la mesure quantitative de la PeCO2 fournie un signal d’alarme précoce pour les accidents anesthésiques potentiellement catastrophiques; 3) l’incidence des accidents augmente avec le temps.

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.

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.

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.

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 infants 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.

Development of a Pediatric Burn Pain and Anxiety Management Program

To facilitate effective management of pain and anxiety, and to permit more objective assessment of changes in this management, a pain and anxiety guideline was developed and has been followed uniformly for 3 years. The guideline describes four patient care categories: (1) ventilated acute, (2) nonventilated acute, (3) chronic acute, and (4) reconstructive. A small and consistent formulary was emphasized. A specific guideline for background, procedural, and transition pain and anxiety management was developed for each patient care category. All pain and anxiety medications given to all acutely burned children admitted to the Institute for 12 consecutive months were recorded, and daily pain and anxiety discomfort scores were noted using a 5-level action-based bedside scoring system. Doses of individual pain and anxiety medications were calculated as mg per kg per patient-day in each category, and all doses were found to be within guideline specifications. The efficacy of the guideline was judged by four discomfort scores: (1) background pain, (2) procedural pain, (3) background anxiety, and (4) procedural anxiety, and were adequate in all patient categories. There were no complications related to overmedication experienced during the interval. Our objective was to develop a guideline for pain and anxiety management that: (1) was safe and effective over a broad range of ages and injury acuities seen in the unit, (2) was explicit in its recommendations, (3) had a limited formulary to optimize staff familiarity with agents used, and (4) took advantage of the presence of a bedside nurse to continuously evaluate efficacy and intervene when needed through dose-ranging. Although many drugs are appropriate, our choices were based on institutional familiarity and simplicity. This process of developing a clear and consistent guideline can be duplicated in any unit.

Persistent ionized hypocalcemia in patients during resuscitation and recovery phases of body burns.

Despite important physiological functions, the fluctuations in plasma ionized calcium concentrations [Ca++] after major thermal injury have not been defined. Measurements of [Ca++] were undertaken in 25 patients of age ranging from 6–75 years, with body surface area burns of 25–85%. Plasma total calcium [Ca], inorganic phosphorus [Pi] and magnesium [Mg++] were also followed. Urinary excretion of the same ions was quantified in nine patients for the first 6 days postburn. The control group consisted of 12 patients who had sustained a similar injury at least 16 months earlier. Significantly low [Ca++] persisted throughout the observation period, despite an average replacement of 0.2 mM/kgμday of CaCl2. The initial hypophosphatemia and hypermagnesemia tended toward normal during the latter phase of the injury. Urinary excretion of the cations was not significantly elevated in the first 6 days postburn. The usual reciprocal relationship between [Ca] and [Pi] was not evident, and there was no correlation between [Ca++] and the size of burn. The use of McLean-Hastings nomogram poorly predicted the [Ca++] from [Ca]. Our data indicate that marked alterations in [Ca++] homeostasis occur after thermal injury. The etiology of hypocalcemia remains to be elucidated; the physiological consequences in terms of hemodynamic function deserve further study.