ZusammenfassungFragestellung: Durch die Einführung von Buprenorphin (BUP, Subutex ) in die Substitutionstherapie von opiatabhängigen Schwangeren fand eine Bereicherung der Therapiemöglichkeiten statt. Die bisher veröffentlichten Ergebnisse zur Buprenorphinsubstitution in der Schwangerschaft beinhalteten keine Auswertung der Umstellungsphase und gaben nur unzureichende Hinweise zum Vorgehen bei der Buprenorphinumstellung von mit Heroin oder Methadon substituierten Schwangeren. Material und Methodik: Seit der Einführung von BUP in das Therapiespektrum der Infektionsambulanz der Klinik für Geburtsmedizin der CharitØ im Juni 2000 wurden von insgesamt 114 opiatabhängigen Schwangeren 33 (29%) in der Schwangerschaft mit BUP substituiert. 27 dieser Patientinnen wurden durch die Ambulanz auf BUP umgestellt, 6 Patientinnen waren bereits mit BUP substituiert. Von den 114 Patientinnen wurde eine Vergleichsgruppe mit 56 opiatabhängigen Patientinnen (49,1 %) ausgewählt, bei denen entsprechend unserer Einschlusskriterien eine Buprenorphinumstellung in der Schwangerschaft möglich gewesen wäre, eine Umstellung jedoch nicht durchgeführt wurde. Die vorliegende Analyse vergleicht die geburtsmedizinischen und neonatalen Ergebnisse von mit BUP substituierten Schwangeren mit den Ergebnissen bei Methadon-(L-Polamidon -) Substitution. Ergebnisse: In der statistischen Analyse zeigen die beiden Vergleichskollektive keine signifikanten demografischen oder anamnestischen Unterschiede, auch der Anteil von Schwangeren Abstract Purpose: With the introduction of buprenorphine (BUP, Subutex ) for the treatment of pregnant opiate addicts the therapeutical spectrum for these patients was enhanced. Current publications showed advantages of BUP compared to methadone but did not explain how the switching of substances could be accomplished. We have evaluated our data to give recommendations on the use of buprenorphine in pregnancy. Material and Methods: Since the introduction of BUP in our therapeutic concept in June 2002 we have treated a total of 114 pregnant opiate addicts. 33 (29 %) of the patients were substituted with BUP. Out of the group of patients not treated with BUP we selected a control-group of 56 patients (49.1%) that met our criteria for BUP treatment but did not switch to BUP for various reasons. The analysis presented here compares obstetrical and neonatological data between the BUP and methadone (L-Polamidon ) group.Results: The statistical analysis shows no significant difference with respect to demographical and obstetrical parameters between the two groups. The number of women with additional consumption of illegal substances is comparable as well. The most important difference is a significantly shorter duration of neonatal care for the group of BUP-exposed neonates compared to the methadone group. Conclusion: Treatment of pregnant opiate addicts with the help of a substitution therapy with buprenorphine is easily accomOriginalarbeit

Infants exposed to opiates antenatally display withdrawal symptoms after birth referred to as neonatal abstinence syndrome (NAS).A total of 366 newborns (166 females, 10 twins) from 361 mothers were diagnosed with NAS from 2000 to 2011 at a single large metropolitan referral center.Retrospective chart review of all newborn infants exposed to opiates in utero.20% were premature (gestational age<37 weeks), 32% were small-for-gestational-age (<10 percentile). 70% of infants (195/278) antenatally exposed to methadone (racemic methadone or levomethadone) required pharmacological treatment for 11 (1-55) days (median; range); however, 45% of infants (28/62) exposed to buprenorphine required pharmacological treatment for a median of only 5 (1-20) days (p=0.014). Pharmacological treatment of infants with phenobarbital (n=189) took a median of 9 (1-53) days, but treatment with morphine (n=39) took 19 (3-55) days (p<0.001). The median duration of hospitalization increased from 11 days in 2000-2004 to 19 days in 2008-2011 (p<0.001). The increased durations of neonatal hospitalization were associated with similar increases in the average dosages of maternal methadone.Use of buprenorphine, rather than methadone, for treatment of opiate-addicted pregnant women is associated with fewer and shorter neonatal withdrawal symptoms. The duration of hospitalization and treatment for NAS has increased over time.

The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

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