R. Schwagmeier

Patient-controlled intranasal analgesia: effective alternative to intravenous PCA for postoperative pain relief

Purpose: To investigate whether the nasal route for fentanyl administration in patient-controlled analgesia (PCA) provides as effective postoperative analgesia as intravenous PCA.Methods: Patient-controlled intranasal or intravenous analgesia with fentanyl was investigated in 48 patients (ASA I – III) on the day of surgery (orthopedic, abdominal or thyroid) in a prospective, randomized, double-blind, double-dummy study. Fentanyl was given in a bolus of 25µg for intranasal and 17.5µg foriv PCA, lockout interval six minutes. The first requested dose was doubled in both groups. Pain intensity (101-point numerical rating scale) and vital parameters were observed at 11 measurement points during the 240 min study. Patients were asked for side effects at every measurement point and for their satisfaction at the end of the study by the same investigator (J.M.).Results: Onset of analgesia, the first reduction in pain intensity on the numerical rating scale, was 21±11 min (range 15 – 45 min) in intranasal and 22±16 min (range 15 – 90 min) iniv PCA. Pain intensity was reduced from 55±11 to 11±10 in the intranasal group and from 53±8 to 11±6 in theiv PCA group. Vital parameters remained stable and side effects were comparable in both groups. The judgement “excellent” or “good” was given by 21 of 23 patients treated intranasally and 24 of 25 patients treated intravenously.Conclusion: Intranasal PCA with fentanyl was an effective alternative toiv PCA in postoperative patients.RésuméObjectif: Vérifier si l’administration de fentanyl par voie nasale, comme analgésie contrôlée par le patient (ACP), procure une analgésie aussi efficace que l’ACP par voie intraveineuse.Méthode: L’analgésie contrôlée par le patient, avec du fentanyl par voie intranasale ou intraveineuse, a fait l’objet d’une étude prospective, randomisée, en double aveugle et double feinte, chez 48 patients (ASA I–III), le jour de l’intervention chirurgicale (orthopédique, abdominale ou thyroïdienne). Le fentanyl a été administré en un bolus de 25µg par voie nasale et de 17,5µg par voie intraveineuse et la période réfractaire a été de six minutes. La première dose demandée a été doublée chez les patients des deux groupes. L’intensité de la douleur (101 à l’échelle d’estimation numérique) et les paramètres vitaux ont été mesurés à 11 reprises pendant les 240 min de l’étude. C’est le même chercheur (J.M.) qui a interrogé les patients sur les effets secondaires lors de chaque mesure et sur leur satisfaction à la fin de l’étude.Résultats: Le délai d’installation de l’analgésie, le temps nécessaire à la première réduction de l’intensité de la douleur selon l’échelle d’estimation numérique, a été de 21±11 min (intervalle de 15–45 min) our l’ACP intranasale et de 22±16 min (intervalle de 15 − 90 min) pour l’ACPiv. L’intensité de la douleur a été réduite de 55±11 à 11±10 dans le groupe intranasal et de 53±8 à 11±6 dans le groupeiv. Les paramètres vitaux sont demeurés stables et les effets secondaires comparables chez les patients des deux groupes. L’analgésie a été jugée «excellente» ou «bonne» par 21 des 23 patients traités avec l’ACP intranasale et par 24 des 25 patients traités avec l’ACP intraveineuse.Conclusion: L’ACP intranasale avec le fentanyl a été une solution de rechange efficace à l’ACPiv en administration postopératoire.

Patient-controlled intranasal analgesia : A method for noninvasive postoperative pain management

Recently, a new device for patient-controlled intranasal analgesia (PCINA) was described, and a pilot study demonstrated promising results with respect to efficacy and patient satisfaction. The present study compares PCINA with intravenous (IV) patient-controlled analgesia (PCA). Fifty orthopedic patients were prospectively studied over an 8-h period on the first day after surgery. The patients were randomly allocated to PCINA group (n = 25) or to an IV PCA group (n = 25). Pain intensity was evaluated at 30-min intervals using a 101-point numerical rating scale. With respect to initial pain intensity, there was no significant intergroup difference. At the 30- to 480-min measurement points pain intensity in the PCINA group (P < 0.0001) and the IV PCA group (P < 0.0001) was significantly less as compared to the initial value. There was no significant intergroup difference in pain intensity. No patient had problems using the PCINA device. The present study demonstrates, that PCINA provides relief of postoperative pain as effectively as IV PCA. (Anesth Analg 1996;83:548-51)

Pharmacokinetics of intranasal alfentanil

STUDY OBJECTIVE To determine the pharmacokinetics of intranasal and intravenous (IV) administrations of alfentanil in 10 healthy volunteers. DESIGN Randomized, prospective, double-blind, placebo-controlled, cross-over trial with at least one week between the two modes of administration. SETTING Healthy volunteers at a university medical center. SUBJECTS 10 healthy, nondrug-dependent volunteers. INTERVENTIONS Alfentanil 0.54 mg was administered either intranasally [with 12 ml of sodium chloride (NaCl) 0.9% IV] or IV (with 12 sprays of NaCl 0.9% intranasally). Each subject was assigned once to the intranasal and once to the IV group. To guarantee a complete elimination of alfentanil, there was a time period of at least one week between the different modes of administration. MEASUREMENTS AND MAIN RESULTS Venous blood was sampled from a cubital vein at 3, 6, 9, 12, 15, 20, 30, 60, and 120 minutes after administration. Alfentanil plasma concentrations were determined by radioimmunoassay. Maximal plasma concentrations were 20.1 ng/ml +/- 7.3 ng/ml after 9 minutes in the intranasal group. At this measurement point, the intranasal alfentanil concentrations were 64.7% (18.7 ng/ml +/- 6.8 ng/ml) of the IV concentrations (28.9 ng/ml +/- 7.9 ng/ml). The calculated bioavailability after intranasal administration was 64.96% +/- 26.3%. CONCLUSIONS This pharmacokinetic study demonstrates a rapid rise in plasma concentrations, as well as a high bioavailability, following the intranasal administration of alfentanil.

Anaesthesia Equipment Patient controlled oral analgesia with morphine

PurposeWhen using strong oral opioids for postoperative pain management, demand titration is desirable. A device for patient controlled oral analgesia (PCORA) and first results of its use for oral titration of morphine are presented.MethodsThe PCORA-device is a modified Baxter-PCA-on-demand system (maximum bolus volume: 0.5 ml; flow rate for filling bolus volume: 0.5 ml · hr−1). The demand PCORA-volumes were measured at specific time intervals and PCORA was compared with customarily prescribed pain therapy (CPPT) for postoperative pain management. On the first post-operative day, 20 orthopaedic ASA I or II patients received, in a randomised, cross-over trial, either PCORA (300 min) followed by CPPT (300 min) (Group I) or vice versa (Group II). The PCORA-device permitted a maximum dose of 15 mg morphine per 60 min and CPPT was performed by the ward doctor or nurse. Pain intensity (101-point numerical rating scale) and side effects were evaluated at 30 min intervals.ResultsThe accuracy of the bolus volume delivered by the PCORA-device was 89.2 ± 0.85% (mean ± SEM), of manufacturer’s specifications. PCORA pain intensity decreased over time whereas CPPT pain intensity did not (P < 0.001). PCORA-morphine requirements were 61.5 ± 5.2 mg (Group I) and 52.5 ± 8.5 mg (Croup II) (NS; mean ± SEM). The handling of the PCORA-device presented no problem to any patient.ConclusionPatient controlled oral analgesia is an effective and non-invasive mode of postoperative pain management. The PCORA-device is reliable and easy to use.RésuméObjectifPour traiter la douleur postopératoire avec des morphiniques puissants, il est désirable d’utiliser une posologie à la demande. On présente ici un dispositif pour l’analgésie orale contrôlée par le patient (PCORA) ainsi que les premiers résultats obtenus avec une posologie de morphine orale.MéthodesLe dispositif PCORA était constitué d’un système de PCA Baxter (bolus maximal en volume: 0,5 ml; vitesse du débit pour réaliser le bolus: 0,5 ml · h−1). Les volumes à la demande fournis par PCORA étaient mesurés à intervalles spécifiques et PCORA était comparé à la prescription antalgique habituelle (méthode CPPT). La première journée postopératoire, 20 patients orthopédiques ASA I et II recevaient aléatoirement et en croisé soit PCORA (300 min) suivi par CPPT (300 min) (groupe I) ou vice-versa (groupe II). Le dispositif PCORA permettait d’administrer une dose maximale de 15 mg de morphine sur 60 min et la CPPT était administrée par un médecin ou une infirmière du service. L’intensité de la douleur (sur une échelle numérique de 101 points) et les effets secondaires étaient évalués aux 30 min.RésultatsLa précision des volumes en bolus délivrés par le dispositif PCORA était à 89,2 ± 0,85% (moyenne ± SEM) des spécifications fournies par le manufacturier. Sous PCORA, l’intensité de la douleur diminuait avec le temps contrairement à la CPPT(P < 0,001). Sous PCORA, les besoins en morphine étaient de 61,5 ± 5,2 mg (groupe I) et 52,5 ± 8,5 (groupe II) (NS; moyenne ± SEM). La manipulation du dispositif de PCORA n’a posé de problèmes à aucun patient.ConclusionL’analgésie orale autocontrôlée par le patient représente une méthode efficace et non effractive de gestion postopératoire de la douleur. Le PCORA est fiable et facile à utiliser.

Self-administered intranasal meperidine for postoperative pain management

Recent studies have demonstrated that intranasal is comparable to intravenous opioid titration in its pain-relieving effect. In these studies, however, the intranasal opioid titration was performed by the investigator, and the treatment period was two hours or less. The purpose of this randomized, prospective study was to investigate whether intranasal opioid administration by the patients themselves for a prolonged postoperative period may be regarded as a therapeutic alternative for postoperative pain management. Forty-four orthopaedic patients were studied over a 12-hr period on the first day after surgery. Twenty-two had free access to intranasal meperidine (nasal group) and were allowed to administer six intranasal puffs (27 mg per dose). The next self-administration was only permitted after a delay of at least ten minutes. Another 22 patients received intermittent subcutaneous meperidine injections (25 or 50 mg) on request (sc group). Pain intensity was recorded at 30-min intervals with the aid of the 101-point numerical rating scale. The pain score was lower in the nasal than in the sc group at the 30, 150 to 330, 420 to 480 and 540 to 600 min measuring points (P = <.0.05). The meperidine requirement was 112.9 ± 81.3 mg in the nasal and 103.4 ± 41.5 mg in the sc group (NS). Two patients in each group complained of nausea and vomiting. Thirteen of the 21 nasal and nine of the 15 sc patients who completed the final questionnaire rated the pain management as excellent or good (NS). Four patients in the nasal group complained of a bitter and burning taste due to meperidine running down the back of the throat. At 14 of the 20 measuring points, better pain relief was achieved by self-administration of intranasal meperidine than by intermittent subcutaneous meperidine injections. The disadvantage of intranasal meperidine is its unpleasant taste if it runs down into the oropharynx. A longlasting opioid with a neutral taste would be preferable.RésuméDes études récentes ont montré que, par la voie nasale, l’effet analgésique des morphiniques est comparable à la voie intraveineuse. Cependant, la dose intranasale était autoadministrée par l’investigateur et la période de traitement que de deux heures ou moins. Cette étude prospective randomisée avait pour objectif de déterminer si l’autoadministration par le patient d’un morphinique par voie nasale sur une période prolongée pouvait constituer une alternative valable pour l’analgésie postopératoire. Quarantequatre patients orthopédiques ont été évalués sur une période de 12 h immédiatement après l’intervention. Le groupe nasal (22 patients) avail de la mépéridine nasale à sa disposition et pouvait s’administrer jusqu’à six bouffées (27 mg par bouffée). La dose suivante n’était permise quaprès un délai d’au moins dix min. Un autre groupe de 22 patients (groupe sc) recevait sur demande des injections souscutanées de mépéridine (25 ou 50 mg). L’intensité douloureuse était évaluée sur une échelle numérique à 101 points. Les scores d’intensité douloureuse ont été moins élévés dans le groupe nasal que dans le groupe sc aux moments 30, 150 à 330, 420 à 480 et à 540 à 600 min (P <0,05). La dose de mépéridine nasale requise a été de 112,9 ± 81,3 mg, et la mépéridine souscutanée de 103,4 ± 41,5 mg (NS). Dans chaque groupe, deux patients se sont plaints de nausées et de vomissements. Treize des 21 patients du groupe nasal et neuf des 15 patients du groupe sc ayant rempli le questionnaire final ont jugé le traitement excellent ou bon (NS). Quatre patients du groupe nasal se sont plaints du goût amer de la mépéridine et de la sensation de brûlure ressentie lorsqu’elle descenda.it dans l’arrièregorge. A 14 des vingt points de mesure, le soulagement de la douleur par autoadministration à été jugé supérieur aux injections intermittentes souscutanées. Le goût désagréable de la mépéridine constitue un désavantage. Un morphinique de longue durée avec un goût agréable serait préférable.

Neue Applikationswege für Opioide

In the last few years great interest has developed in new modes of opioid administration; oral transmucosal, transdermal, peripheral, and nasal administration.Oral transmucosal administration of fentanyl citrate (OTFC) has most often been used for premedication in children. Meanwhile, studies on the use of OTFC in cancer patients for postoperative pain management have also been published. While OTFC may have a limited role in postoperative pain management, it may prove very helpful in the management of incident and breakthrough cancer pain. Patient acceptance is high, and the onset of action is relatively rapid.Transdermal administration of fentanyl (TTS fentanyl) has been extensively examined, especially in postoperative patients. Patient acceptance is high, and TTS-fentanyl-related side-effects (e.g. mild erythema at the site of application) are minor. Application is performed at 72-h intervals. Kinetics are stable with repeated dosing, and serum concentrations approach steady state with the first dose. The slow rise/decline in fentanyl plasma concentration with patch application/removal makes it less well suited for postoperative pain management. However, TTS fentanyl seems to be a promising mode of opioid administration for cancer patients.-Recent papers have unequivocally demonstrated a peripheral antinociceptive effect oflocally applied opioids, especially in inflamed tissue. However, the results of clinical investigations are equivocal so far: about half the reports demonstrate an analgesic effect of peripherally administered opioids, and the other half, not.Intranasal administration was introduced for premedication in children, but benzodiazepines seem to be the better and safer choice. Nonetheless, intranasal opioids guarantee a rapid rise in opioid plasma concentrations as well as a rapid onset of pain relief. This mode of administration seems to be especially suitable for the treatment of acute pain syndromes, such as breakthrough cancer pain or incident pain. Patient acceptance is high, and no local problems were reported.ZusammenfassungSeit einigen Jahren besteht zunehmendes Interesse an neuen Applikationswegen und-formen für Opioide. Untersucht werden insbesondere die buccale, die transdermale, die peripher-lokale und die nasale Opioidapplikation. Diebuccale Opioidgabe wurde vor allem im Rahmen von Prämedikationsstudien untersucht. Inzwischen liegen auch erste Studien zur buccalen Opioidgabe bei chronischen Tumorschmerzen und bei postoperativen Schmerzen vor. Diese Applikationsform scheint vor allem zur Therapie akuter Schmerzspitzen bei chronischen Karzinomschmerzen geeignet. Die Patientenakzeptanz gegenüber der buccalen Gabe ist hoch. Dietransdermale Fentanylgabe (TTS-Fentanyl) ist inzwischen gut untersucht. Vorteile dieser nichtinvasiven Applikationsform sind die ca. 72 Stunden dauernde Wirkung und eine hohe Patientenakzeptanz. TTS-Fentanyl scheint weniger zur Therapie akuter postoperativer Schmerzen, dagegen aber gut zur Behandlung langdauernder, chronischer Karzinomschmerzen geeignet. Zurperipher-lokalen Applikation von Opioiden liegen inzwischen etliche Publikationen vor. Aber nur in ca. der Hälfte dieser Studien konnte eine gute Schmerzlinderung nachgewiesen werden. Erfolgversprechend scheint vor allem die lokale Opioidapplikation im Bereich von entzündetem Gewebe zu sein. Dieintranasale Opioidgabe ist durch einen sehr schnellen Wirkungsbeginn ausgezeichnet. Die nasale Applikationsform scheint sich vor allem zur Therapie akuter Schmerzpspitzen im Rahmen chronischer Tumorschmerzen anzubieten. Es konnte eine hohe Patientenakzeptanz nachgewiesen werden.AbstractIn the last few years great interest has developed in new modes of opioid administration; oral transmucosal, transdermal, peripheral, and nasal administration.Oral transmucosal administration of fentanyl citrate (OTFC) has most often been used for premedication in children. Meanwhile, studies on the use of OTFC in cancer patients for postoperative pain management have also been published. While OTFC may have a limited role in postoperative pain management, it may prove very helpful in the management of incident and breakthrough cancer pain. Patient acceptance is high, and the onset of action is relatively rapid.Transdermal administration of fentanyl (TTS fentanyl) has been extensively examined, especially in postoperative patients. Patient acceptance is high, and TTS-fentanyl-related side-effects (e.g. mild erythema at the site of application) are minor. Application is performed at 72-h intervals. Kinetics are stable with repeated dosing, and serum concentrations approach steady state with the first dose. The slow rise/decline in fentanyl plasma concentration with patch application/removal makes it less well suited for postoperative pain management. However, TTS fentanyl seems to be a promising mode of opioid administration for cancer patients.—Recent papers have unequivocally demonstrated a peripheral antinociceptive effect oflocally applied opioids, especially in inflamed tissue. However, the results of clinical investigations are equivocal so far: about half the reports demonstrate an analgesic effect of peripherally administered opioids, and the other half, not.Intranasal administration was introduced for premedication in children, but benzodiazepines seem to be the better and safer choice. Nonetheless, intranasal opioids guarantee a rapid rise in opioid plasma concentrations as well as a rapid onset of pain relief. This mode of administration seems to be especially suitable for the treatment of acute pain syndromes, such as breakthrough cancer pain or incident pain. Patient acceptance is high, and no local problems were reported.

Ein neues Gerät zur patientenkontrollierten intranasalen Analgesie

IntroductionIt has been demonstrated that intranasal opioid titration has a rapid onset of action and can provide satisfactory management of postoperative pain [10, 12, 14]. In these studies the intranasal titration was carried out by the investigator. Self-administration of an opioid intranasally by patients requires a spray bottle with safety precautions of an equivalent standard to those offered by an intravenous PCA device. We describe a device for patient-controlled intranasal analgesia (PCINA) that meets these safety requirements.MethodsThe Baxter PCA on demand system consists of a mechanically driven infusor, a flow restrictor, and a patient control module for bolus administration. The flow restrictor provides a flow rate of 5 ml/h or 2 ml/h. This Baxter intravenous PCA system has been subjected to a slight modification to adapt it for PCINA. The patient control module has a bolus volume of 0.5 ml and in this modification it is attached, instead of to an intravenous line, to a narrow, 26-gauge plastic cannula with the needle tip removed (Fig. 1). To check the accuracy of the volume delivered, three PCINA devices with a flow rate of 5 ml/h (filling time of 6 min for the 0.5-ml bolus volume) and three PCINA devices with a flow rate of 2 ml/h (filling time of 15 min for the 0.5-ml bolus volume) were examined at defined time intervals. The PCINA devices were filled with distilled water and the volume demanded was immediately determined by means of a high-precision scale. Three determinations of the volumes delivered were performed. In an initial unblinded pilot observation in five orthopaedic patients, PCINA (for a 4-h period) was compared with the conventionally prescribed pain medication (for a subsequent 5-h period). For intranasal opioid administration, fentanyl (1 ml=0.05 mg) was used. At every evaluation point, pain intensity was evaluated with the aid of a 101-point numerical rating scale (0 = no pain, 100 = worst pain possible). At the end of both examination periods (PCINA/conventionally prescribed pain medication), overall patient satisfaction with the method of pain management experienced was evaluated (graded: very good, good, satisfactory, bad, very bad, not acceptable).ResultsThe volumes delivered from the three PCINA devices with a flow rate of 5 ml/h (PCINA device 6′) and from the three PCINA devices with a flow rate of 2 ml/h (PCINA device 15′) are presented in Fig. 4. The subjective pain intensities measured with the 101-point numerical rating scale are demonstrated in Fig. 5. The patients used 0.28±0.097 mg fentanyl (0.15–0.45 mg) during the 4-h period of PCINA. No patients had any difficulty using the PCINA device. No technical problems arose with any of the devices. No patient complained of intranasal pain or burning during or after nasal administration. At the end of the study overall patient satisfaction with PCINA was judged as very good (2 patients), good 2 patients) or satisfactory (1 patient). The relief obtained with the customarily prescribed pain medication was judged as satisfactory (1 patient) or bad (4 patients).ConclusionWe conclude that the PCINA device presented fulfils the PCA device safety requirements. The bolus volume delivered by the device is precise and follows the manufacturer’s specifications for flow rate and bolus volume. Initial

New modes of opioid administration.

In the last few years great interest has developed in new modes of opioid administration; oral transmucosal, transdermal, peripheral, and nasal administration.Oral transmucosal administration of fentanyl citrate (OTFC) has most often been used for premedication in children. Meanwhile, studies on the use of OTFC in cancer patients for postoperative pain management have also been published. While OTFC may have a limited role in postoperative pain management, it may prove very helpful in the management of incident and breakthrough cancer pain. Patient acceptance is high, and the onset of action is relatively rapid.Transdermal administration of fentanyl (TTS fentanyl) has been extensively examined, especially in postoperative patients. Patient acceptance is high, and TTS-fentanyl-related side-effects (e.g. mild erythema at the site of application) are minor. Application is performed at 72-h intervals. Kinetics are stable with repeated dosing, and serum concentrations approach steady state with the first dose. The slow rise/decline in fentanyl plasma concentration with patch application/removal makes it less well suited for postoperative pain management. However, TTS fentanyl seems to be a promising mode of opioid administration for cancer patients.-Recent papers have unequivocally demonstrated a peripheral antinociceptive effect oflocally applied opioids, especially in inflamed tissue. However, the results of clinical investigations are equivocal so far: about half the reports demonstrate an analgesic effect of peripherally administered opioids, and the other half, not.Intranasal administration was introduced for premedication in children, but benzodiazepines seem to be the better and safer choice. Nonetheless, intranasal opioids guarantee a rapid rise in opioid plasma concentrations as well as a rapid onset of pain relief. This mode of administration seems to be especially suitable for the treatment of acute pain syndromes, such as breakthrough cancer pain or incident pain. Patient acceptance is high, and no local problems were reported.ZusammenfassungSeit einigen Jahren besteht zunehmendes Interesse an neuen Applikationswegen und-formen für Opioide. Untersucht werden insbesondere die buccale, die transdermale, die peripher-lokale und die nasale Opioidapplikation. Diebuccale Opioidgabe wurde vor allem im Rahmen von Prämedikationsstudien untersucht. Inzwischen liegen auch erste Studien zur buccalen Opioidgabe bei chronischen Tumorschmerzen und bei postoperativen Schmerzen vor. Diese Applikationsform scheint vor allem zur Therapie akuter Schmerzspitzen bei chronischen Karzinomschmerzen geeignet. Die Patientenakzeptanz gegenüber der buccalen Gabe ist hoch. Dietransdermale Fentanylgabe (TTS-Fentanyl) ist inzwischen gut untersucht. Vorteile dieser nichtinvasiven Applikationsform sind die ca. 72 Stunden dauernde Wirkung und eine hohe Patientenakzeptanz. TTS-Fentanyl scheint weniger zur Therapie akuter postoperativer Schmerzen, dagegen aber gut zur Behandlung langdauernder, chronischer Karzinomschmerzen geeignet. Zurperipher-lokalen Applikation von Opioiden liegen inzwischen etliche Publikationen vor. Aber nur in ca. der Hälfte dieser Studien konnte eine gute Schmerzlinderung nachgewiesen werden. Erfolgversprechend scheint vor allem die lokale Opioidapplikation im Bereich von entzündetem Gewebe zu sein. Dieintranasale Opioidgabe ist durch einen sehr schnellen Wirkungsbeginn ausgezeichnet. Die nasale Applikationsform scheint sich vor allem zur Therapie akuter Schmerzpspitzen im Rahmen chronischer Tumorschmerzen anzubieten. Es konnte eine hohe Patientenakzeptanz nachgewiesen werden.AbstractIn the last few years great interest has developed in new modes of opioid administration; oral transmucosal, transdermal, peripheral, and nasal administration.Oral transmucosal administration of fentanyl citrate (OTFC) has most often been used for premedication in children. Meanwhile, studies on the use of OTFC in cancer patients for postoperative pain management have also been published. While OTFC may have a limited role in postoperative pain management, it may prove very helpful in the management of incident and breakthrough cancer pain. Patient acceptance is high, and the onset of action is relatively rapid.Transdermal administration of fentanyl (TTS fentanyl) has been extensively examined, especially in postoperative patients. Patient acceptance is high, and TTS-fentanyl-related side-effects (e.g. mild erythema at the site of application) are minor. Application is performed at 72-h intervals. Kinetics are stable with repeated dosing, and serum concentrations approach steady state with the first dose. The slow rise/decline in fentanyl plasma concentration with patch application/removal makes it less well suited for postoperative pain management. However, TTS fentanyl seems to be a promising mode of opioid administration for cancer patients.—Recent papers have unequivocally demonstrated a peripheral antinociceptive effect oflocally applied opioids, especially in inflamed tissue. However, the results of clinical investigations are equivocal so far: about half the reports demonstrate an analgesic effect of peripherally administered opioids, and the other half, not.Intranasal administration was introduced for premedication in children, but benzodiazepines seem to be the better and safer choice. Nonetheless, intranasal opioids guarantee a rapid rise in opioid plasma concentrations as well as a rapid onset of pain relief. This mode of administration seems to be especially suitable for the treatment of acute pain syndromes, such as breakthrough cancer pain or incident pain. Patient acceptance is high, and no local problems were reported.

[A device for patient-controlled intranasal analgesia (PCINA).].

IntroductionIt has been demonstrated that intranasal opioid titration has a rapid onset of action and can provide satisfactory management of postoperative pain [10, 12, 14]. In these studies the intranasal titration was carried out by the investigator. Self-administration of an opioid intranasally by patients requires a spray bottle with safety precautions of an equivalent standard to those offered by an intravenous PCA device. We describe a device for patient-controlled intranasal analgesia (PCINA) that meets these safety requirements.MethodsThe Baxter PCA on demand system consists of a mechanically driven infusor, a flow restrictor, and a patient control module for bolus administration. The flow restrictor provides a flow rate of 5 ml/h or 2 ml/h. This Baxter intravenous PCA system has been subjected to a slight modification to adapt it for PCINA. The patient control module has a bolus volume of 0.5 ml and in this modification it is attached, instead of to an intravenous line, to a narrow, 26-gauge plastic cannula with the needle tip removed (Fig. 1). To check the accuracy of the volume delivered, three PCINA devices with a flow rate of 5 ml/h (filling time of 6 min for the 0.5-ml bolus volume) and three PCINA devices with a flow rate of 2 ml/h (filling time of 15 min for the 0.5-ml bolus volume) were examined at defined time intervals. The PCINA devices were filled with distilled water and the volume demanded was immediately determined by means of a high-precision scale. Three determinations of the volumes delivered were performed. In an initial unblinded pilot observation in five orthopaedic patients, PCINA (for a 4-h period) was compared with the conventionally prescribed pain medication (for a subsequent 5-h period). For intranasal opioid administration, fentanyl (1 ml=0.05 mg) was used. At every evaluation point, pain intensity was evaluated with the aid of a 101-point numerical rating scale (0 = no pain, 100 = worst pain possible). At the end of both examination periods (PCINA/conventionally prescribed pain medication), overall patient satisfaction with the method of pain management experienced was evaluated (graded: very good, good, satisfactory, bad, very bad, not acceptable).ResultsThe volumes delivered from the three PCINA devices with a flow rate of 5 ml/h (PCINA device 6′) and from the three PCINA devices with a flow rate of 2 ml/h (PCINA device 15′) are presented in Fig. 4. The subjective pain intensities measured with the 101-point numerical rating scale are demonstrated in Fig. 5. The patients used 0.28±0.097 mg fentanyl (0.15–0.45 mg) during the 4-h period of PCINA. No patients had any difficulty using the PCINA device. No technical problems arose with any of the devices. No patient complained of intranasal pain or burning during or after nasal administration. At the end of the study overall patient satisfaction with PCINA was judged as very good (2 patients), good 2 patients) or satisfactory (1 patient). The relief obtained with the customarily prescribed pain medication was judged as satisfactory (1 patient) or bad (4 patients).ConclusionWe conclude that the PCINA device presented fulfils the PCA device safety requirements. The bolus volume delivered by the device is precise and follows the manufacturer’s specifications for flow rate and bolus volume. Initial

Self-Administered Intranasal Meperidine for Postoperative Pain Management

Recent studies have demonstrated that intranasal is comparable to intravenous opioid titration in its pain-relieving effect. In these studies, however, the intranasal opioid titration was performed by the investigator, and the treatment period was two hours or less. The purpose of this randomized, prospective study was to investigate whether intranasal opioid administration by the patients themselves for a prolonged postoperative period may be regarded as a therapeutic alternative for postoperative pain management. Forty-four orthopaedic patients were studied over a 12-hr period on the first day after surgery. Twenty-two had free access to intranasal meperidine (nasal group) and were allowed to administer six intranasal puffs (27 mg per dose). The next self-administration was only permitted after a delay of at least ten minutes. Another 22 patients received intermittent subcutaneous meperidine injections (25 or 50 mg) on request (sc group). Pain intensity was recorded at 30-min intervals with the aid of the 101-point numerical rating scale. The pain score was lower in the nasal than in the sc group at the 30, 150 to 330, 420 to 480 and 540 to 600 min measuring points (P = < 0.05). The meperidine requirement was 112.9 +/- 81.3 mg in the nasal and 103.4 +/- 41.5 mg in the sc group (NS). Two patients in each group complained of nausea and vomiting. Thirteen of the 21 nasal and nine of the 15 sc patients who completed the final questionnaire rated the pain management as excellent or good (NS).(ABSTRACT TRUNCATED AT 250 WORDS)