Transmission of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through infant feeding and early care practices: A systematic review.

BACKGROUND: Perinatal practices such as breast-feeding, kangaroo mother care, rooming-in, and delayed cord clamping have varied by institution during the COVID-19 pandemic. The goal of this systematic review was to examine the success of different practices in preventing viral transmission between SARS-CoV-2 positive mothers and their infants. METHODS: Electronic searches were performed in the Ovid MEDLINE, Ovid Embase, Cochrane Library, EBSCOhost CINAHL Plus, Web of Science, and Scopus databases. Studies involving pregnant or breastfeeding patients who tested positive for SARS-CoV-2 by RT-PCR were included. Infants tested within 48 hours of birth who had two tests before hospital discharge were included. Infants older than one week with a single test were also included. RESULTS: Twenty eight studies were included. In the aggregated data, among 190 breastfeeding infants, 22 tested positive for SARS-CoV-2 (11.5%), while 4 of 152 (2.63%) among bottle-fed (Fisher's exact test p = 0.0006). The positivity rates for roomed in infants (20/103, 19.4%) were significantly higher than those isolated (5/300, 1.67%) (P < 0.0001). There was no significant difference in positivity rate among infants who received kangaroo care (25%vs 9%, p = 0.2170), or delayed cord clamping (3.62%vs 0.9%, p = 0.1116). CONCLUSIONS: Lack of robust studies involving large patient population does not allow meaningful conclusions from this systematic review. Aggregated data showed increased positivity rates of SARS-CoV-2 among infants who were breast fed and roomed-in. There were no differences in SARS-CoV-2 positivity rates in infants received skin to skin care or delayed cord clamping.

Plasmonic nanocone arrays for rapid and detailed cell lysate surface enhanced Raman spectroscopy analysis.

In this work, we develop, fabricate, and characterize a plasmonic nanocone array surface enhanced Raman spectroscopy (SERS) substrate with a uniform enhancement factor on the micron scale for qualitative and quantiative cell and cell lysate analysis. This work demonstrates how SERS substrates can be used as cell-based biosensors given that the enhancement factor of the substrate is sufficient for Raman detection and that the uniformity is high over the applicable surface area. These requirements allow accurate and quantitative comparisons between nonuniform samples under varying biochemical conditions. We apply the developed SERS substrate for Raman measurements and mapping of HeLa cells and cell lysate. This method is used for identification of UV-induced damage and detection of nanomolar concentrations of methylated guanine spiked in cell lysate samples.

Label-free cell-substrate adhesion imaging on plasmonic nanocup arrays.

Cell adhesion is a crucial biological and biomedical parameter defining cell differentiation, cell migration, cell survival, and state of disease. Because of its importance in cellular function, several tools have been developed in order to monitor cell adhesion in response to various biochemical and mechanical cues. However, there remains a need to monitor cell adhesion and cell-substrate separation with a method that allows real-time measurements on accessible equipment. In this article, we present a method to monitor cell-substrate separation at the single cell level using a plasmonic extraordinary optical transmission substrate, which has a high sensitivity to refractive index changes at the metal-dielectric interface. We show how refractive index changes can be detected using intensity peaks in color channel histograms from RGB images taken of the device surface with a brightfield microscope. This allows mapping of the nonuniform refractive index pattern of a single cell cultured on the plasmonic substrate and therefore high-throughput detection of cell-substrate adhesion with observations in real time.

Buprenorphine exposure in infants of opioid-dependent mothers at birth.

BACKGROUND: Buprenorphine, a partial opioid agonist used in treating opioid dependence, is not approved in Australia for use in pregnancy. Nevertheless, many pregnant women choose to remain on the drug. AIM: To investigate cord/maternal transfer ratios for buprenorphine and norbuprenorphine in women at delivery. METHODS: Maternal and cord serum samples were collected from 10 maternal-infant pairs at delivery. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Maternal and infant demographic information was collected. Linear regression was used to assess the relationship between maternal and cord measurements. RESULTS: Median (interquartile range) maternal age was 27 (23.8-32) years, with 90% of the women on buprenorphine before pregnancy. Median infant birthweight was 3148 (3088-3545) g and 60% of infants had neonatal abstinence requiring admission to a neonatal intensive care unit for a median of 8.5 (2.5-16.3) days. Median maternal buprenorphine daily dose was 8.5 mg (range 1-28 mg). Mean (95% confidence interval) cord serum concentrations of buprenorphine and norbuprenorphine were 0.4 (0.3-0.5) µg/L and 1.2 (0.9-1.4) µg/L, respectively. Mean maternal concentrations of buprenorphine and norbuprenorphine were 1.0 (0.6-1.4) µg/L and 1.2 (0.9-1.4) µg/L, respectively. Mean cord/maternal ratios were 0.43 (0.36-0.5) for buprenorphine and 0.53 (0.43-0.63) for norbuprenorphine. Maternal buprenorphine and norbuprenorphine concentrations and ratio of buprenorphine/norbuprenorphine explained 85.7, 69.6 and 94.4%, respectively, of variation in the corresponding cord concentrations. CONCLUSION: Usual therapeutic doses of buprenorphine administered to pregnant women resulted in low concentrations of buprenorphine and norbuprenorphine in maternal serum and a low transfer to the fetal circulation (cord plasma) at birth.

Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment.

OBJECTIVE: The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. STUDY DESIGN: Seven pregnant opioid-dependent women taking buprenorphine (median, 7 mg/day; range, 2.4-24 mg) and who intended to breastfeed were recruited. After lactation was established, several milk samples were collected from each subject over a 24-hour dose interval, and buprenorphine and norbuprenorphine concentrations were measured by liquid chromatography-tandem mass spectrometry. The average concentration (C(avg)) across the dose interval was estimated as for both buprenorphine and norbuprenorphine (as buprenorphine equivalents). Absolute infant dose (AID), defined as C(avg) × daily milk intake, and relative infant dose (RID), defined as 100×AID/weight-adjusted maternal daily dose, via milk were calculated, assuming a milk intake of 0.15 L/kg/day. The infant's health and progress were assessed directly and by questionnaire on the study day. RESULTS: Mean (95% confidence interval) norbuprenorphine concentration in milk and AID values (1.94 [0.79-3.08] µg/L and 0.29 [0.12-0.46] µg/kg/day, respectively) were approximately half those for buprenorphine (3.65[1.61-5.7] µg/L and 0.55 [0.24-0.85] µg/kg/day, respectively). Similarly, the mean RID values were 0.18% (0.11-0.25%) for norbuprenorphine and 0.38% (0.23-0.53%) for buprenorphine. The breastfed infants showed no adverse effects, were all in good health, and were progressing as expected. CONCLUSION: Thus the dose of buprenorphine and norbuprenorphine received via milk is unlikely to cause any acute adverse effects in the breastfed infant.

Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal.

AIMS: To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). METHODS: The data set included 78 escitalopram overdose events (median dose, 140mg [10-560mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. RESULTS: A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUC(i) /dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (α= 0.35). The heart rate corrected QT interval (QT(c) ) was linearly dependent on predicted escitalopram concentration [slope = 87ms/(mgl(-1) )], using a hypothetical effect-compartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200mg. CONCLUSIONS: There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal.

Duloxetine transfer across the placenta during pregnancy and into milk during lactation.

OBJECTIVE: Duloxetine is an efficacious antidepressant; however, its safety during the perinatal period is uncertain. The objective of this study was to assess the transfer across the placenta and provide data on infant exposure to duloxetine via breast milk. METHODS: A multiparous 31-year-old woman with recurrent melancholic depression had responded poorly to previous antidepressants, but had a full remission on duloxetine. She elected to remain on duloxetine for her third pregnancy and while breastfeeding. She gave birth to a healthy term infant and there were no adverse events noted for the infant exposed to duloxetine. Duloxetine concentration was measured chromatographically in maternal and infant serum collected at birth, and in maternal milk and plasma and infant plasma 18 days later, (C/M) concentration ratio was calculated. Absolute and relative infant doses via milk were estimated and the percent drug in infant versus mother's plasma was calculated. RESULTS: Cord/maternal serum concentration ratio for duloxetine was 0.12. Absolute infant dose via milk was 7.6 µg/L and relative infant dose was 0.81%. The ratio of drug in the infant's plasma to that in maternal plasma during lactation also gave a 0.82% infant exposure estimate. CONCLUSIONS: The low C/M ratio suggests a limited transfer across the placenta. The relative infant dose via milk was low by comparison to most other antidepressants, and this estimate confirmed the amount of drug in infant plasma during lactation. Our data suggest that duloxetine may be used in pregnancy and lactation for selected patients in whom other antidepressants have not been successful.

Effective clearance of Ara-U the major metabolite of cytosine arabinoside (Ara-C) by hemodialysis in a patient with lymphoma and end-stage renal failure.

PURPOSE: We report that hemodialysis clears Ara-U from the blood after high-dose Ara-C treatment in a patient with lymphoma and end-stage renal failure. METHODS: The patient received two doses of Ara-C 1 g/m(2) 24 h apart and was hemodialyzed at about 6 h after each dose and subsequently as per her usual dialysis schedule. Multiple blood samples were collected after dosing. Blood and dialyzate were also collected from the dialysis circuit during a second identical treatment cycle. Ara-C and its metabolite Ara-U in plasma and dialyzate were measured chromatographically, and the data subjected to pharmacokinetic analysis. RESULTS: The distribution and elimination half-lives, steady-state volume of distribution and clearance values were 0.5 h, 7 h, 181 L and 307 l/h for Ara-C and 4.1 h, 34 h, 118 L and 2.64 l/h for Ara-U, respectively. The dialysis sessions immediately after the first and second doses cleared 39 and 52% (as Ara-U) of the respective Ara-C doses. Some 63% of Ara-U in plasma was extracted by dialysis. The patient showed no signs of neurotoxicity or other drug-related adverse effects. CONCLUSION: Hemodialysis is very effective in clearing Ara-U from the plasma in renal failure, and this maneuver could easily be used routinely to prevent Ara-U accumulation and minimize adverse effects in patients with renal failure.

Estimation of rac-amisulpride transfer into milk and of infant dose via milk during its use in a lactating woman with bipolar disorder and schizophrenia.

This case describes the transfer of the antipsychotic drug amisulpride into milk and the estimation of infant exposure via breastfeeding. The dyad investigated was a 28-year-old lactating woman and her 13-month-old daughter. The woman had been taking 400 mg of amisulpride daily for 9 days and provided eight milk samples and one blood sample over a 24-hour dose interval. Amisulpride concentrations in these samples were measured by high-performance liquid chromatography, and infant dose was calculated by standard methods. The infant's health and progress were evaluated by a neonatal pediatrician. Transfer of amisulpride into milk was high, with a milk:plasma distribution ratio of 19.5 (5,188 µg/L in milk and 266 µg/L in plasma). The average amisulpride concentration in milk was 3,562 µg/L, which, when multiplied by an average milk intake of 0.15 L/kg/day, gave an absolute infant dose of 534 µg/kg/day. The relative infant dose was 10.7% of the maternal weight-adjusted dose (5,000 µg/kg/day), which is slightly above the usual 10% safety recommendation. The infant was in good health with an appropriate Denver development score for her age. She showed no acute drug-related adverse effects. Given that the infant had already benefited from 13 months of breastfeeding, that amisulpride has potential adverse effects, and that its relative infant dose was 10.7%, we recommended cessation of breastfeeding in the near-term.

Estimation of desvenlafaxine transfer into milk and infant exposure during its use in lactating women with postnatal depression.

This study characterises the extent of desvenlafaxine transfer into milk and provides data on infant exposure to desvenlafaxine via breast milk in ten women with postnatal depression and their breastfed infants. Desvenlafaxine concentration in milk and plasma was measured chromatographically in milk and in maternal and infant plasma collected at steady state. Theoretic and relative infant doses via milk were estimated and the per cent drug in infant versus mother's plasma was calculated. Theoretic infant dose via milk was 85 (53-117) µg kg(-1) day(-1) (mean and 95% confidence interval) and relative infant dose was 6.8% (5.5-8.1%). The ratio of drug in infant/maternal plasma also gave an infant exposure estimate of 4.8% (3.5-6.2%) for all ten infants and 5.3% (4.2-5.7%) in the eight infants who were exclusively breastfed. No adverse effects were seen in the infants. The relative infant dose was similar to that for previous studies using venlafaxine and was supported by a separate exposure measure using the ratio of drug in the infant's plasma relative to that in the mother's plasma. The theoretic infant dose of desvenlafaxine was 41-45% of that for venlafaxine and its metabolite desvenlafaxine in previous studies, reflecting the lower recommended maternal dose for desvenlafaxine. Although our data for desvenlafaxine use in lactation are encouraging and there are supporting data from venlafaxine studies, more patients and their infants need to be studied before the safety of desvenlafaxine as a single therapeutic agent can be fully assessed.

Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies.

OBJECTIVE: To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies. ANIMALS: 8 IR ponies. PROCEDURES: Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined. RESULTS: Mean±SD elimination half-life (t1/2) of metformin was 11.7±5.2 hours, maxima plasma concentration was 748±269 ng/mL at 54±32 minutes, mean area under the curve was 355±92 microg.h/mL, and apparent clearance was 90.6±28.1 mL/min/kg. The Css was 122±22 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance.

Assessment of infant dose through milk in a lactating woman taking amisulpride and desvenlafaxine for treatment-resistant depression.

This study presents the case of a 35-year-old breastfeeding mother who delivered her fourth child 5 months previously and was prescribed 100 mg amisulpride twice daily and 250 mg desvenlafaxine in the morning for treatment-resistant depression. Arriving at this regimen took approximately 2 months postbirth. Because she was keen to continue breastfeeding her infant, and published data on the use of amisulpride and desvenlafaxine were very limited, the clinical team sought assistance from the therapeutic drug monitoring laboratory to quantify infant dose-exposure to guide consideration of continuing breastfeeding. A sampling schedule for milk and plasma from mother and plasma from her infant was agreed and drug concentrations were measured by high-performance liquid chromatography. Absolute (theoretic) infant dose (µg/kg/d) was calculated as the product of the average concentration in milk and an assumed milk intake of 0.15 L/kg/day (294 mg/kg/day for desvenlafaxine and 183 mg/kg/day for amisulpride), and relative infant dose was estimated as absolute infant dose expressed as a percentage of the maternal dose in µg/kg/day (7.8% for desvenlafaxine and 6.1% for amisulpride). Consistent with the infant being partially breastfed, the ratio of drug in the infant's plasma to that in mother's plasma was lower at 1.7% for desvenlafaxine and 3.9% for amisulpride. A pediatric assessment of the infant found achievement of expected developmental progress for age and no detectable drug-related adverse effects. Assessing the safety of breastfeeding was difficult because it involved simultaneous use of two drugs for which there was limited previous experience. However, after discussion of the infant dose-exposure data and lack of adverse effects, the mother elected to continue partial breastfeeding for the next few months. The clinical team plans a reassessment of the infant's progress in 3 months.

Use of duloxetine in pregnancy and lactation.

OBJECTIVE: To report a case of a woman who used duloxetine during pregnancy and breast-feeding. CASE SUMMARY: A 29-year-old woman was treated with duloxetine for depression during the second half of an uncomplicated gestation. She gave birth at term to a healthy female infant. A cord blood sample was obtained at birth. The mother continued the antidepressant while exclusively breast-feeding her infant. One month later, we collected blood and milk samples from the mother and a single blood sample from the infant. All samples were analyzed for the presence and concentrations of duloxetine. DISCUSSION: Duloxetine crosses the placenta at term and is excreted into breast milk. No evidence of developmental or other type of toxicity was observed in the infant at birth or during the first 32 days after birth. The published literature detailing human pregnancy experience with this antidepressant is limited to 11 cases in which women became pregnant while taking duloxetine. In 10 cases, the drug was discontinued when pregnancy was diagnosed and no outcome data were reported. In the eleventh case, an infant exposed to duloxetine 90 mg/day developed neonatal behavioral syndrome. One study examined the excretion of duloxetine into breast milk, but the mothers discontinued nursing for the study. In the present case, no adverse effects from exposure to the drug in milk were noted in the exclusively breast-fed infant. The possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded because long-term follow-up has not been conducted in infants exposed to duloxetine in utero or during nursing. CONCLUSIONS: No developmental toxicity or other signs of toxicity were observed in an infant exposed to duloxetine during the second half of gestation and during breast-feeding in the first 32 days after birth. However, the possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded.

Transfer of metyrapone and its metabolite, rac-metyrapol, into breast milk.

Metyrapone, an inhibitor of corticosteroid biosynthesis, is used in the diagnosis and treatment of adrenocortical hyperfunction. The authors describe the excretion of metyrapone and its metabolite, rac-metyrapol, in milk from a lactating woman requiring metyrapone treatment (250 mg 4 times daily). At steady state, the average concentrations in milk and absolute and relative infant doses were 11 microg/L, 1.7 microg/kg/d, and 0.02%, respectively, for metyrapone, and 48.5 microg/L, 7.3 microg/kg/d, and 0.08%, respectively, for rac-metyrapol. The findings suggest that maternal metyrapone use during breastfeeding is extremely unlikely to be a significant risk for the breastfed infant.

The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose.

The aim of this work was to investigate the pharmacokinetics (PK) of venlafaxine in overdose and the effects of single-dose activated charcoal (SDAC) and whole-bowel irrigation (WBI), alone or in combination, as methods of decontamination. The data included 339 concentration-time points from 76 venlafaxine overdose events (median dose 2,625 (150-13,500 mg)); 69 were slow-release doses. SDAC, WBI, a combination of both, or no decontamination were administered to patients as decided by the treating clinician. The data were modeled using WinBUGS (Windows Bayesian Inference Using Gibbs Sampling). A one-compartment model with first-order input and elimination provided an adequate description of the data. SDAC increased clearance (CL) of venlafaxine by 35%, and SDAC and WBI combined reduced the fraction absorbed by 29%. However, the latter produced a greater reduction in maximum plasma concentration (C(max)) for a similar drop in area under the plasma concentration-time curve (AUC). Both SDAC alone, and a combination of SDAC and WBI, decreased the AUC after venlafaxine overdose, but the combination may be more beneficial because it reduces peak concentrations to a greater extent.

Placental transfer of SSRI and SNRI antidepressants and effects on the neonate.

INTRODUCTION: We investigated placental transfer and neurobehavioural effects in neonates exposed to citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine or sertraline (SSRI's), or to venlafaxine (an SNRI). METHODS: Women receiving antidepressants during pregnancy and their neonates were studied. Cord and maternal drug concentrations were measured at birth and in the neonates plasma on day 3. Neonates were also assessed using a range of neurobehavioral tests and compared to controls. RESULTS: Median cord/maternal distribution ratio was 0.7-0.86 (range) for SSRIs, 0.72 for the SNRI venlafaxine and 1.08 for the O-desmethyl metabolite. Neonatal abstinence scores were significantly higher (p<0.05) in exposed infants than controls on day 1. Brazelton scores for habituation, social-interactive, motor and autonomic clusters, and serotonin scores were significantly greater (p<0.05) in exposed infants. DISCUSSION: Transfer of SSRIs and SNRIs across the placenta was substantial. Neonates developed mild behavioral symptoms in the early perinatal period but these were self-limiting and similar for both SSRIs and the SNRI venlafaxine.

Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete. WHAT THIS STUDY ADDS: We have provided data on the transplacental transfer of chloroquine and desethylchloroquine in Melanesian women (n = 19), measured transfer of these drugs into breast milk (n = 16) and estimated absolute and relative infant doses for the breastfed infant. The data for desethylchloroquine are novel. In all three areas we have significantly increased both quantity and quality of the available database. AIMS: To investigate the transfer of chloroquine and its major bioactive metabolite desethylchloroquine across the placenta and into breast milk. METHODS: In Papua New Guinea, chloroquine (CQ; 25 mg base kg(-1)) is recommended for prophylaxis of malaria during pregnancy, and at the Alexishafen Health Centre women are routinely prescribed CQ at the time of delivery. Fetal-cord and maternal serum samples were collected at delivery (n = 19) and milk samples were collected from day 3 to day 17-21 after delivery (n = 16). CQ and its primary active metabolite desethylchloroquine (DECQ) were quantified by high-performance liquid chromatography. For both CQ and DECQ cord/maternal ratios (C/M) were calculated to characterize placental transfer, and infant exposure via milk was estimated by standard methods. RESULTS: The median (interquartile range) C/M was 1.1 (0.9, 1.6) for CQ and 1.2 (0.5, 1.8) for DECQ. The average concentration in milk over the time of sampling was 167 microg l(-1) (27, 340) for CQ and 54 microg l(-1) (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 microg kg(-1) day(-1) (7, 50) and 15 microg kg(-1) day(-1) (4, 26), and 2.3% (0.5, 3.6) and 1.0% (0.4, 2.0) for CQ and DECQ (as CQ equivalents), respectively. CONCLUSION: Infant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.

Disposition and clinical outcome after intraperitoneal meperidine and ropivacaine administration during laparoscopic surgery.

BACKGROUND: Limited evidence supports the efficacy of intraperitoneal (IP) meperidine or local anesthetic for postoperative analgesia. Our study aims were to investigate analgesic efficacy and to quantify the plasma concentrations of meperidine and ropivacaine after IP administration. The null hypothesis was that there was no significant difference among groups for dynamic pain in the first 24 h after major abdominal laparoscopic surgery. METHODS: This double-blind, five parallel group, placebo-controlled, two-center trial randomized 250 women having laparoscopic surgery to receive IP meperidine 50 or 100 mg (groups M50 and M100), ropivacaine 150 mg (group R150), meperidine 50 mg and ropivacaine 150 mg (group M50R150), all with intramuscular saline, or IP saline, with intramuscular meperidine 50 mg (group C). The primary outcome was pain during recovery. A pharmacokinetic profile of the drugs was obtained. RESULTS: There were no significant differences among groups for mean (sd) dynamic pain scores in the postoperative care unit (2.2 [2.8], 2.5 [3.3], 1.6 [2.5], 2.6 [3.2], 2.7 [3.2] for groups C, M50, M100, R150, and M50R150, P = 0.50) or thereafter. There were no significant differences among groups for pain scores at rest, IV morphine use, recovery characteristics and patient satisfaction. After IP administration of meperidine 50 mg the plasma concentration (median average 55-60 microg/L) was approximately half that of an equivalent intramuscular dose (median average 113 mug/L). CONCLUSIONS: Compared with systemic opioid, IP meperidine and ropivacaine, alone or in combination, did not produce better pain relief or opioid dose-sparing after laparoscopic surgery.

Effect of open-chest surgery in the lateral position on blood propofol concentration during target-controlled infusion of propofol.

Our research hypothesis was that single lung ventilation during thoracic surgery in the lateral position increases the blood concentration of propofol during target-controlled infusion. Thirty adult patients in two tertiary referral hospitals undergoing open-chest surgery were studied. Anaesthesia was induced and maintained with propofol using a Diprifusor (Graseby 3500) computer-controlled pump set to deliver a blood concentration of 4 tg.ml(-1). Blood samples were taken with the patient positioned in (1) the supine position 20 minutes after induction (supine); (2) the lateral position just prior to one-lung ventilation (lateral); (3) the lateral position five minutes after commencing one-lung ventilation (OLV5) and (4) the lateral position 20 minutes after commencing one-lung ventilation (OLV20). Propofol concentrations were determined by high performance liquid chromatography. The target-controlled infusion target level was maintained at 4 microg.ml(-1) during the study period for all cases. The mean (SD) propofol blood concentration (microg.ml(-1)) at each stage was 5.5 (1.5) supine, 5.3 (1.1) lateral, 5.3 (1.2) OLV5 and 5.1 (1.2) OLV20. Repeated measures ANOVA showed an F value 1.9, lambda 5.5 and P value 0.15. Post hoc analysis did not identify a significant difference between the sample times. During target-controlled infusion of propofol, mean blood propofol concentrations did not change significantly from those obtained with the patient supine after up to 50 minutes in the lateral position during thoracic surgery, or 20 minutes after commencing one-lung ventilation.