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OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion

Neuraxial opioids as analgesia in labour, caesarean section and hysterectomy: A questionnaire survey in Sweden [version 2; referees: 2 approved]

Background: Neuraxial opioids improve labour analgesia and analgesia after caesarean section (CS) and hysterectomy. Undesirable side effects and difficulties in arranging postoperative monitoring might influence the use of these opioids. The aim of the present survey was to assess the use of intrathecal and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A questionnaire was sent to all anaesthetic obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 of 47 (68%) units responded representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units use intrathecal morphine, the most common dose of which was 100 μg (17/21). Intrathecal fentanyl (10-20 μg) was used by 21 units and sufentanil (2.5 -10 μg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural fentanyl (50-100 μg) or sufentanil (5-25 μg) were commonly used (25/32), and 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose. Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 μg as the most common dose (9/32). Postoperative monitoring was organized in adherence to the National Guidelines; the patient is monitored postoperative care or an obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward. Risk of respiratory depression/difficult to monitor was a reason for not using intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in CS and hysterectomy, but is still restricted in some units because of the concern for respiratory depression and difficulties in monitoring

Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion

Inflammatory mediators.

<p><b>Statistics</b>: Values are expressed as median and range.</p><p>WBC  =  White blood cell count (x10⁹/L); IL-1 =  Interleukin 1(pg/ml); TNF-α =  Tumor Necrosis Factor-α (pg/ml); LPS =  Lipopolysaccharide; iNO =  Inhaled nitric oxide.</p>1<p>within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Circulatory variables.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Kidney function.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours (urine output: no baseline value, volume collected over time, from 12 to 30 hours).</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences versus LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Study protocol.

<p>The scale bar depicts time in hours.</p

Respiratory variables.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Changes in serum creatinine levels over time, unit = µmol/L. LPS = lipopolysaccharide, IV steroid = intravenous hydrocortisone, iNO = inhaled nitric oxide.

<p>Values are shown as median and range. Data have been collected at 0, 12, 24 and 30(*: p = 0.02). No significances between treatment groups (IV steroid, iNO, IV steroid + iNO) and LPS alone were noted.</p