Olivier Gall

Fixed 50% Nitrous Oxide Oxygen Mixture for Painful Procedures: A French Survey

Objective. Although the equimolecular mixture of oxygen and nitrous oxide (EMONO) seems a good choice to relieve procedure-related pain in children, it has not been accepted everywhere. In France, the rapid spread of its use has elicited suspicion and doubts regarding its safety. To assess the use and the safety of this gas mixture in the pediatric settings in France, we conducted a national survey. Methodology. Centers that had accepted a nation- wide invitation to participate in the survey filled out a questionnaire after each EMONO administration during a 2-month study. Procedure and inhalation characteristics, as well as pain evaluations and side effects, were reported. Results. One thousand nineteen EMONO inhalations from 31 centers that agreed to participate in this 2-month survey were analyzed. Median (range) age was 6.4 (0–18) years. Four percent (46) of children were 12 months old or younger, 29% (295) were 5 years old or younger, 45% (459) were 6 to 10 years old, and 26% (265) were older than 10 years of age. The procedures performed with EMONO inhalation were: lumbar punctures (286), bone marrow aspirations (BMA; 231), laceration repairs (215), minor procedures (75), minor surgery (53), punctures (49), fractures (45), dental care (43), and pulmonary endoscopy (22). Nine percent of procedures were undertaken without the presence of a physician; the child being observed only by the attending nurse. A drug association was noted in 182 (17.9%) of procedures: midazolam (63%), acetaminophen (18%), nalbuphine (8.5%), hydroxyzine (5%), flunitrazepam (2%), chlorazepate (2%), morphine (1%), and lorazepam (.5%). EMLA cream (Astra) was applied in 98.6% of lumbar punctures, 93.7% of BMA, and 54.2% of punctures including lymph nodes, hematoma, or renal biopsies. Lidocaine infiltration was performed in 51% of minor surgery procedures, 40% of laceration repairs, and 28% of BMA. The inhalation system included a whistle, a scented mask, and a nonrebreathing respiratory valve in 48.9%, 71.2%, and 78.3% of the patients, respectively. Initial physical restraint was needed in 18.2% of all the patients. Inhalation refusal was noted in 129 (12.7%) children; of these, 53 had an alternative method of analgesia (EMLA or lidocaine infiltration), 15 had no other analgesia, and in the remaining 61, EMONO inhalation was maintained against the childs will. Median (interquartile) inhalation length was 4 (3–5) minutes before starting the procedure and 6 (6–15) minutes for the total inhalation. Median (interquartile) procedural pain evaluations were 9 (0–30) for children on a 0 to 100 visual analog scale, 1 (0–3) for both nurses and parents on a 0 to 10 numerical scale. Median (interquartile) procedural pain as evaluated by nurses for the 3 most frequent procedures were 0 (0–2) for lumbar punctures, 2 (0–4) for bone marrow aspiration, and 2 (0–4) for laceration repair. Comparison of pain assessed by nurses in children 3 years old or younger and those older than 3 years of age showed a median (range) score of 2 (0–10) versus 1 (0–10), respectively. Pain self-assessment was completed in 647 children 6 years of age or older. Median (interquartile) children pain assessments were as follows: lumbar puncture (5; 0–20), bone marrow aspiration (12.5; 0–40), laceration repair (12; 0–40), minor procedures (18; 0–32), minor surgery (10; 0–35), punctures (0; 0–18), fracture (15; 0–30), dental care (20; 0–40), and pulmonary endoscopy (15; 0–30). Ninety-three percent of the 647 children who were able to answer the question said they would accept EMONO analgesia if a new procedure were to be performed. Behavioral reactions during procedures varied with age of the child; cry was observed in 44.1%, 24.4%, 12.9%, and 11.2% of children 3 years or younger, 4 to 6 years, 7 to 10 years, and 11 years or older, respectively. Physical restraint was necessary in 34.2%, 22%, 13.5%, and 8.4% of children aged 3 years or younger, 4 to 6 years, 7 to 10 years, and 11 years or older, respectively. Staff satisfaction regarding EMONO efficacy was as follows: very satisfied (56.7%), satisfied (31.3%), not satisfied (8.6%), and very unsatisfied (3.3%). Minor side effects were observed during 381 (37%) inhalations. These side effects were euphoria (20.1%), change in visual or auditory perception (7.0%), dreams (5.7%), nausea and vomiting (3.7%), deep sedation (2.1%), paresthesia (1.7%), dizziness (1.6%), restlessness (1.5%), nightmares and hallucinations (1.2%), and miscellaneous (1.9%). All side effects were transient and vanished within 5 minutes after removing the inhalation device. No serious side effects were noted. Conclusions. This survey shows that EMONO is used to provide analgesia in a great variety of procedures. Although analgesia obtained during procedures is good, this gas mixture is not efficacious in all patients. Therefore, physicians should quickly detect failures to switch to another analgesic approach. The best results are obtained in children 3 years of age or older. Although minor effects are frequent during EMONO inhalation, its use seems very safe because no single serious side effect was noted during this study. This helpful method is still underused, and it should be readily available in each emergency and pediatric department.

Adverse events of premixed nitrous oxide and oxygen for procedural sedation in children

In France, administration of premixed 50% nitrous oxide and oxygen for procedural sedation is under close supervision by the French Drug Agency before final approval for use. We have examined the frequency of adverse events in children sedated with 50% nitrous oxide and oxygen over a broad range of non-specialised facilities. A mean of 0.33% (SD 0.10) children had major adverse events. Thus, premixed 50% nitrous oxide and oxygen seems to be a safe option for procedural sedation in children.

Analgesic effect of low-dose intrathecal morphine after spinal fusion in children.

Background This study was designed to assess the postoperative analgesic effect of low-dose intrathecal morphine after scoliosis surgery in children. Methods Thirty children, 9–19 yr of age, scheduled for spinal fusion, were randomly allocated into three groups to receive a single dose of 0 (saline injection), 2, or 5 &mgr;g/kg intrathecal morphine. After surgery, a patient-controlled analgesia device (PCA) provided free access to additional intravenous morphine. Children were monitored for 24 h in the postanesthesia care unit. Results The three groups were similar for age, weight, duration of surgery, and time to extubation. The time to first PCA demand was dose-dependently delayed by intrathecal morphine. The first 24 h of PCA morphine consumption was 49 ± 17, 19 ± 10, and 12 ± 12 mg (mean ± SD) in the saline, 2 &mgr;g/kg morphine, and 5 &mgr;g/kg morphine groups, respectively. Pain scores at rest were significantly lower over the whole study period after 2 and 5 &mgr;g/kg intrathecal morphine than after saline, but there was no difference between intrathecal doses. Pain scores while coughing and the incidence of side effects were similar in the three groups. Conclusions These data demonstrate that low-dose intrathecal morphine supplemented by PCA morphine provides better analgesia than PCA morphine alone after spinal fusion in children. The doses of 2 and 5 &mgr;g/kg seem to have similar effectiveness and side-effect profiles, whereas a reduction of intraoperative bleeding was observed in patients who received 5 &mgr;g/kg but not 2 &mgr;g/kg intrathecal morphine.

Dorsal horn convergent neurones: negative feedback triggered by spatial summation of nociceptive afferents

&NA; In order to investigate the effects of spatial summation on the spinal transmission of nociceptive information, we compared in intact and spinal anaesthetized rats, responses of lumbar convergent neurones elicited by noxious heat stimuli applied to areas of the body much greater in size than their individual excitatory receptive fields, located distally on the hindpaw. Twenty‐four neurones were recorded in each group of animals. For each neurone, 4 successive immersions of increasing areas (1.9–18 cm2) of the ipsilateral hindpaw in a 48°C water bath (15‐sec duration) were performed with 10‐min intervals in a randomized and balanced order. In intact animals, the responses of convergent neurones progressively decreased when the area of noxious thermal stimulation reached and then exceeded approximately twice the area of their individual excitatory receptive fields. This decrease was highly significant for 18 cm2 which represents approximately 10‐fold the mean of the receptive field areas. Such a phenomenon was not observed for neurones recorded in spinal animals although their excitatory receptive field areas were not significantly different. These results suggest that the activation of a large population of nociceptive afferents triggers supraspinally mediated negative feed‐back loop modulating the responses of convergent neurones.

Procedural pain in children: evidence-based best practice and guidelines

d f d a c i a c rocedural pain is frequently encountered in children either during an emergency or mangement of their disease. Applying the concept of vidence-based medicine to the problem of proceural pain in children is challenging. First, the umber of annual publications dealing with pain in hildren is growing and, second, procedural pain ncompasses a wide variety of different situations hat may differ by type of procedure and/or age roup. This review will address the following quesions: should we do something to reduce or supress procedural pain in children; which procedures re included; what will influence the choice of therpy; are therapeutic interventions supported by efcacy and safety data; is there any evidence for ombining drugs and nonpharmacological methds; and how to reduce the risk of analgesia-related omplications? Only large cohort surveys, randomzed trials, and systematic reviews will be considred in the following review. The neonatal period ill not be considered.

Pain management in neonates

Multiple lines of evidence suggest an increased sensitivity to pain in neonates. Repeated and prolonged pain exposure may affect the subsequent development of pain systems, as well as potentially contribute to alterations in long-term development and behavior. Despite impressive gains in the knowledge of neonatal pain mechanisms and strategies to treat neonatal pain acquired during the last 15 years, a large gap still exists between routine clinical practice and research results. Accurate assessment of pain is crucial for effective pain management in neonates. Neonatal pain management should rely on current scientific evidence more than the attitudes and beliefs of care-givers. Parents should be informed of pain relief strategies and their participation in the health care plan to alleviate pain should be encouraged. The need for systemic analgesia for both moderate and severe pain, in conjunction with behavioral/environmental approaches to pain management, is emphasized. A main sources of pain in the neonate is procedural pain which should always be prevented and treated. Nonpharmacological approaches constitute important treatment options for managing procedural pain. Nonpharmacological interventions (environmental and preventive measures, non-nutritive sucking, sweet solutions, skin–skin contact, and breastfeeding analgesia) can reduce neonatal pain indirectly by reducing the total amount of noxious stimuli to which infants are exposed, and directly, by blocking nociceptive transduction or transmission or by activation of descending inhibitory pathways or by activating attention and arousal systems that modulate pain. Opioids are the mainstay of pharmacological pain treatment but there are other useful medications and techniques that may be used for pain relief. National guidelines are necessary to improve neonatal pain management at the institutional level, individual neonatal intensive care units need to develop specific practice guidelines regarding pain treatment to ensure that all staff are familiar with the effects of the drugs being used and to guarantee access and safe administration of pain treatment to all neonates.

Sedation and analgesia for procedures outside the operating room in children.

There has been a dramatic increase in the number of procedures that are conducted in children in which sedation is now considered beneficial. In many institutions, however, resources and personnel have not been recruited to address this increase in demand. In most institutions, anaesthesiology departments are not able to provide anaesthesia for all procedures that are performed outside the operating theatre, and alternative solutions are needed. Recent research includes attempts to decrease the time required to induce sedation and to recover from it, and development of new organizational models to improve the safety of procedural sedation.

Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.

BACKGROUND Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. METHODS Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. CONCLUSIONS Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.

Disposition of children with burns in emergency departments in Île de France.

The majority of burn injuries are managed by emergency departments (EDs), which are the pivotal axis in patient assessment. The aim of this study was to investigate the discharge destination of children with burn injuries presenting to EDs in Île de France. Therefore, a postal questionnaire was sent to 91 EDs. The number of children with burns and their discharge status after passing through the ED in 2005, as well as the clinical positions of practitioners involved, the discharge destination of children, and the conditions resulting in a transfer to a burn center were assessed. Forty-six EDs replied to the questionnaire. Pediatric burns corresponded to 0.63% of pediatric visits in EDs. The rates of admission (7.8%) and transfer (1.9%) were low. Larger EDs had a higher admission rate and a lower rate of transfer. The need for advice from a burn center remained constant as well as the transfer rate to a burn center (both around 14%), irrespective of the size of the ED. Reasons for transfer agreed with data in the literature. More than 3200 children were registered with burns in half of the regions EDs during 2005. The majority of burns were not severe, as demonstrated by the low number of admissions and transfers, and most children were cared for locally in nonspecialized settings. Nevertheless, the relationship between burn centers and all EDs, not just the large one, needs to be strengthened to improve the quality of care given to these children.

Sommation spatiale et codage médullaire de l’information nociceptive

RésuméLes stimulations nociceptives punctiformes généralement utilisées au cours des études de la nociception chez l’animal sont à l’évidence très différentes des lésions tissulaires, parfois étendues, rencontrées en pratique clinique. Nous avons tenté de préciser le rôle de la sommation spatiale dans l’intégration médullaire de l’information nociceptive en étudiant les effets d’une gamme de stimulations thermiques nociceptives intéressant des surfaces croissantes (1.9 à 18 cm2), dont l’intensité et la durée étaient par ailleurs constantes. Des neurones à convergence possédant un champ périphérique excitateur situé sur l’extrémité de la patte postérieure ipsilatérale ont été enregistrés au niveau lombaire chez des rats anesthésiés. La fréquence de décharge des neurones augmente avec la taille du stimulus lorsque de petites surfaces sont concernées mais décroissent lorsque la surface de stimulation dépasse 4.8 cm2. Cette décroissance, a priori paradoxale, résulte de la mise en jeu de contrôles inhibiteurs descendants car elle n’est pas observée chez des animaux dont la moelle cervicale a été préalablement sectionnée.Des expériences de sections, effectuées à différents niveaux du tronc cérébral ont permis de démontrer que les structures cérébrales impliquées dans ces rétrocontrôles négatifs sont confinées à la partie la plus caudale du bulbe. Ces phénomènes ne sont pas en relation avec l’activation de certains contrôles descendants connus pour moduler la transmission spinale des influx nociceptifs mais impliquant la substance grise périaqueducale et la région rostrale et ventro-médiane du bulbe qui inclut notamment le noyau Raphé Magnus. Ils présentent en revanche plusieurs analogies avec les Contrôles Inhibiteurs Diffus Nociceptifs.Nous avons enfin pu montre dans une troisième série d’expérience que ces rétrocontrôles sont bloqués par une faible dose de morphine (1 mg/kg). Cette dose était assez faible pour ne pas exercer d’effet direct sur la transmission des messages nociceptifs au niveau spinal.Ainsi, lorsqu’un foyer nociceptif est suffisamment étendu il déclenche une boucle de rétrocontrôle négatif mettant en jeu des neurones de la partie la plus caudale du bulbe. Ces résultats pourraient expliquer le fait clinique, souvent observé, qu’il est généralement difficile de corréler l’∈ndue d’une lésion tissulaire avec l’intensité de la douleur ressentie par le patient. Ils suggèrent en outre que lorsqu’un foyer douloureux est étendu, les doses de morphine administrées au patient pour le soulager doivent être suffisantes pour exercer un effet spinal direct.SummaryClinical pain involves the simultaneous activation of large population of spinal afferents. Thus spatial summation may represent an important and somewhat neglected aspect of the processing of nociceptive information. The current experiments were designed to investigate how convergent neurones of the lumbar dorsal horn encode noxious heat stimuli applied to their receptive field and also to much larger adjacent areas.In a first series of experiments, we compared, in intact and spinal anaesthetised rats, the responses of lumbar convergent neurones elicited by stimuli involving a wide range of surface areas of the ipsilateral hindpaw (1.9 to 18 cm2). In intact animals, increasing the stimulus area resulted in a progressive decrease of neuronal responses, when stimulus area increased beyond 4.8 cm2. In contrast., in spinal animal, increasing the stimulus area induced a slight but non significant increase of firing rates. It was concluded that spatial summation, as the result of stimultaneous activation of a large population of noci-responsive neurones, triggers inhibitory mechanisms that are probably supraspinally mediated.Another series of experiments, performed in acute brainstem-transected animals., provided evidence that these inhibitory controls are integrated in the most caudal part of the medulla. The inhibitory controls triggered by spatial summation are thus independeant of the modulating systems organised within the rostral ventromedial and those involving more rostral brainstem structures. In contrast they share common features with diffuse noxious inhibitory controls.A third series of experiments was conducted to assess how different systemic doses of morphine might interfere with the ability of convergent neurones to encode stimulus area. A dose of 1 mg/kg of morphine, wich had no effect on the responses elicited by the 1.9 cm2 stimulus, paradoxically enhanced the thermal responses of convergent neurones when the nociceptive stimulus covered a large surface area. The depressant effects of a 10 mg/kg dose were reduced when the stimulus was applied over 18 cm2 as opposed to 1.9 cm2. Such effects are difficult to explain in terms of accepted pharmacodynamical concepts and may reflect an, opioid-induced depression of the descending inhibitory influences triggered by spatial summation.In summary, spatial summation triggers a supraspinally mediated negative feedback loop modulating the output of convergent neurones, From a clinical point of view these results might explain the classical lack of one to one correspondance between the extent of injury and the intensity of pain or suffering. These results also provide a neurophysiological basis for positive relationship between opioid requirements and the spatial extent of a painful injury.