Update of recommendations for Analgosedation in pediatric intensive care unit.

Effective and adequate therapy to control pain and stress are essential in managing children in Pediatric Intensive Care Unit (PICU) undergoing painful invasive procedures, this should be, but is not yet, one of our main aims. Aware that this difficult mission must be pursued in a systematic, multimodal and multitasking way, the Studying Group on Analgosedation in PICU from the Italian Society of Neonatal and Paediatric Anesthesia and Intensive Care (SARNePI) is providing its recommendations.

Spinal versus peripheral effects of adjunct clonidine: comparison of the analgesic effect of a ropivacaine-clonidine mixture when administered as a caudal or ilioinguinal-iliohypogastric nerve blockade for inguinal surgery in children.

BACKGROUND: The adjunctive use of clonidine to local anaesthetics has been reported to enhance analgesia both after spinal and peripheral administration. However, no attempt has been made to compare spinal and peripheral application of clonidine in the same surgical context in order to further explore the mechanism for the analgesic action of clonidine when administered together with local anaesthetics. METHODS: Using a prospective, randomized, observer-blinded study design, 40 patients, aged 1-7 years, who were undergoing elective surgery for inguinal hernia repair or orchidopexy, were randomly allocated to receive either a caudal block (group C: n = 20; ropivacaine 0.2%, 1 ml.kg-1 + clonidine 2 micro g.kg-1) or an ilioinguinal-iliohypogastric nerve block (group I: n = 20; ropivacaine 0.2%, 0.4 ml.kg-1 + clonidine 2 micro g.kg-1) following the induction of a standardized sevoflurane based anaesthetic. Postoperative analgesia [maximum Objective Pain Scale (OPS) score and requirement for supplemental analgesia] and sedation (three-point scale) were assessed at predetermined intervals during the first 24 h postoperatively. RESULTS: Fourteen children in group I and nine children in group C did not require rescue analgesia (P = 0.17). No difference in maximum OPS scores could be detected between the two study groups. The mean time to full recovery regarding sedation was 149 min and 153 min in groups C and I, respectively. CONCLUSIONS: This pilot study demonstrates a trend for better postoperative analgesia following peripheral administration of clonidine compared with central application. However, the main mechanism for the adjunct analgesic effect of clonidine when administered together with local anaesthetics requires further study.

Ropivacaine-clonidine combination for caudal blockade in children.

BACKGROUND: Adding clonidine to weak ropivacaine solutions (<0.2%) could potentially enhance analgesia as well as further reduce the risk for unwanted motor blockade. The aim of the present study was to compare the postoperative pain-relieving quality of a ropivacaine 0.1%-clonidine mixture to that of plain ropivacaine 0.2% following caudal administration in children. METHODS: In a prospective, observer-blinded fashion, 40 ASA 1 paediatric patients undergoing subumbilical surgery were randomly allocated to receive a caudal injection of either plain ropivacaine 0.2% (1 ml/kg) (R0.2) or a mixture of ropivacaine 0.1% with clonidine 2 microg/kg (1 ml/kg) (R0.1C). Objective pain scale score and need for supplemental analgesia were used to evaluate analgesia during the first 24 h postoperatively. Residual postoperative sedation was also assessed. RESULTS: A significantly higher number of patients in the R0.1C group (18/20) could be managed without supplemental analgesia during the first 24 h postoperatively compared to the R0.2 group (11/20) (P=0.034). Both the degree and the duration of postoperative sedation was similar in both groups. No signs of postoperative motor blockade were observed. CONCLUSIONS: The combination of clonidine (2 microg/kg) and ropivacaine 0.1% is associated with an improved quality of postoperative analgesia compared to plain 0.2% ropivacaine. The improved analgesic quality of the clonidine-ropivacaine mixture is achieved without causing any significant degree of postoperative sedation.

Clonidine-mepivacaine mixture vs plain mepivacaine in paediatric surgery.

In a double-blind study, 42 children, aged 1-10, undergoing general subumbilical surgery, were randomly allocated to two groups; they received, via caudal extradural, 1% mepivacaine 7 mg.kg-1 and normal saline 1 ml (Group 1) and a mixture of 1% mepivacaine 7 mg.kg-1 plus clonidine 2 micrograms.kg-1 and normal saline up to 1 ml (Group 2) respectively. No significant difference was noticed in age, weight, duration of surgery and onset time of anaesthesia, blood pressure, heart rate and oxygen saturation. Mean duration of analgesia (evaluated with 'Broadman objective pain scale') was 143 min for Group 1 and 218 min for Group 2 (P < 0.05); the time of sedation (evaluated with a sedation score) was statistically longer in Group 2 (172 min vs 89 min in Group 1). This longer sedation is due both to the longer analgesia and partially to a side effect of clonidine. In conclusion the addition of 2 micrograms.kg-1 of clonidine to mepivacaine prolongs the duration of caudal analgesia in children.

Evaluation of the ovarian cancer antigen, Ca-125, as a tumor marker.

The presence of the Ca-125 antigen was tested in the serum of 46 patients with ovarian cancer in order to determine the prognostic value of preoperative levels and its usefulness for monitoring the clinical response in longitudinal studies; survival (S) and progression-free survival (PFS) were also evaluated. In our series, the specificity of the assay in normal subjects and in patients with benign gynecological diseases is 99.3 and 73.2% respectively, and the sensitivity is 91.9%. Preoperative Ca-125 levels are not correlated with S and PFS, whereas an advantage in S and PFS is clearly shown for patients in whom the marker level decreases after treatment. Serial determinations of Ca-125 serum levels provide a reliable test to assess response to therapy and to predict disease progression.

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

High dose cisplatin after failure of polychemotherapy containing cisplatin in ovarian cancer. Preliminary results.

A substantial percentage of patients with advanced ovarian cancer will progress or relapse after platinum-based front therapies and will require salvage chemotherapy. In order to evaluate feasibility and effectiveness of high dose platinum (HD-CDDP) nine patients with ovarian cancer were treated with HD-CDDP while progressing after conventional doses of the same drug. Cisplatin 40 mg/M2 d. 1----5 q. 28 days, was administered with forced chloruresis for a total of fifteen cycles. Preliminary results show a promising 44.4% response rate with acceptable toxicity: only one patient had to discontinue treatment because of severe combined toxicity including infection, mucositis, shaking tremors, ototoxicity and palmar hyperkeratosis.

Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for advanced ovarian cancer.

A combination chemotherapy including cisplatin, 25 mg/m2 on Days 1,8; methotrexate, 30 mg/m2 on Day 1; and 5-fluorouracil, 600 mg/m2 on Day 1 has been evaluated in 28 previously untreated and 10 pretreated patients with advanced ovarian cancer after debulking surgery when feasible. The pathological response rates (complete + partial responses) were 69.2 and 50% in untreated and pretreated patients, respectively. Overall 24-month survival and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A significant difference in survival and PFS is evident between patients with less and more than 2 cm residual disease and between responders (CR + PR) versus nonresponders. No renal toxicity was induced and no cycles had to be delayed because of hemathologic toxicity.

[Radioimmunoassay of SP1 in obstetrics and gynecological oncology]. / Dosaggio radioimmunologico della SP1 nella pratica ostetrica e nella oncologia ginecologica.

The authors by means of radioimmunoassay analyze SP1 values in selected obstetric and oncological samples. Seven amniotic fluid samples showed various degrees of positivity, but not strictly correlated to the gestational age (previous analysis by immunodiffusion were always negative). SP1 concentrations in ectopic pregnancy confermed similar investigations by other authors. In the oncological field only one serum was highly positive (440 ng/ml); negativity of others could be due to the long time of storage. The SP1 was assayed using a sperimental kit supplied by Boehringwerke A.G. (Marburg, W.G..). Assay procedure: preparation of a standard curve (7 - 440 ng/ml) from which the unknown SP1 content was determinated. Reaction time: 16 - 24 h/20 degrees C (first incubation) and 0.5 - 4 h/20 degrees C (second incubation).