Patient Preparation with Esomeprazole Is Comparable to Ranitidine in Meckel Diverticulum Scintigraphy.

To localize ectopic gastric mucosa in patients with unexplained gastrointestinal bleeding and diagnose a Meckel diverticulum, 99mTc-pertechnetate imaging is the standard procedure. H2 inhibitor pretreatment enhances the sensitivity of the scan by reducing washout of 99mTc activity from the intestinal lumen. We aim to provide evidence of the effectiveness of the proton pump inhibitor esomeprazole as an ideal substitute for ranitidine. Methods: The scan quality for 142 patients who underwent a Meckel scan during a period of 10 y was evaluated. The patients were pretreated with ranitidine orally or intravenously before a switch to a proton pump inhibitor after ranitidine was no longer available. Good scan quality was characterized by the absence of 99mTc-pertechnetate activity in the gastrointestinal lumen. The effectiveness of esomeprazole to diminish 99mTc-pertechnetate release was compared with the standard treatment using ranitidine. Results: Pretreatment with intravenous esomeprazole resulted in 48% of scans with no 99mTc-pertechnetate release, 17% with release either in the intestine or in the duodenum, and 35% with 99mTc-pertechnetate activity both in the intestine and in the duodenum. Evaluation of scans obtained after oral ranitidine and intravenous ranitidine showed absence of activity in both intestine and duodenum in 16% and 23% of the cases, respectively. The indicated time to administer esomeprazole before starting the scan procedure was 30 min, but a delay of 15 min did not negatively influence the scan quality. Conclusion: This study confirms that esomeprazole, 40 mg, when administered intravenously 30 min before a Meckel scan, enhances the scan quality comparably to ranitidine. This procedure can be incorporated into protocols.

Dosing Therapeutic Radiopharmaceuticals in Obese Patients.

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.

Impact of external cooling with icepacks on 68Ga-PSMA uptake in salivary glands.

BACKGROUND: External cooling of the salivary glands is advised to prevent xerostomia in lutetium-177-PSMA treatment for advanced prostate cancer. Since evidence addressing this subject is sparse, this study aims to determine impact of icepacks application on uptake in salivary glands. Eighty-nine patients referred for gallium-68-PSMA PET/CT for (re)staging of prostate cancer were prospectively included. Twenty-four patients were scanned with unilateral (solely left-sided) icepacks; 20 with bilateral icepacks; 45 without icepacks. Icepacks were applied approximately 30 minutes prior to tracer injection. PET/CT acquisition started 1 hour postinjection. Radiotracer uptake was measured in the parotid- and submandibular glands. RESULTS: When comparing the intervention group with the control group, uptake in the left parotid gland significantly differed: SUVmax: 11.07 ± 3.53 versus 12.95 ± 4.16; p = 0.02. SUVpeak: 9.91 ± 3.14 versus 11.45 ± 3.61; p = 0.04. SUVmax and SUVpeak were reduced with 14.52% and 13.45%. All other SUV values did not significantly differ. Patients with bilateral icepacks showed no significant differences in PSMA uptake compared to the control group (all: p > 0.05). Intra-patient analysis revealed some significant differences in SUVmax and SUVpeak between the cooled and non-cooled parotid gland (SUVmax: 11.12 ± 3.71 versus 12.69 ± 3.75; p = 0.00. SUVpeak: 9.93 ± 3.32 versus 11.25 ± 3.25; p = 0.00). CONCLUSIONS: Impact of icepacks on PSMA uptake seems to be limited to the parotid glands. As clinical relevance of these findings is debatable, structural application of icepacks in the setting of lutetium-177 PSMA therapy needs careful consideration.

Antenatal Maternal Antidepressants Drugs Affect S100B Concentrations in Fetal-Maternal Biological Fluids.

INTRODUCTION: Antidepressant treatment during pregnancy is speedily increasing in developed countries and this phenomenon has occurred without firm evidence on safety and/or efficacy. AIMS: The present study investigated from mid-trimester of pregnancy up to 24 hours after birth the pattern of a brain damage marker, namely S100B, in maternal fetal and neonatal biological fluids of pregnant women and their newborns antenatally treated by antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRI). METHODS: we conducted an observational study on 75 pregnant women treated in the mid -third trimester by antidepressant drugs and 231 healthy pregnancies. S100B concentrations were measured at 7 predetermined monitoring time-points before, during and after treatment in maternal, fetal and neonatal biological fluids and correlated with neurological follow-up at 7 days from birth. RESULTS: In SSRI group S100B concentrations were significantly higher in SSRI than controls (P<0.001, for all) in maternal blood, in amniotic fluid, in arterial and venous cord blood and at 24-h from birth. Highest (P<0.05) S100B levels were found in SSRI infants showing major neurological symptoms at 7-d follow-up. CONCLUSION: The present data on increased S100B levels in maternal, fetal and neonatal biological fluids suggest that SSRI administration although beneficial to the mother, presents some risks for the infant.

Antenatal maternal antidepressants drugs affect Activin A concentrations in maternal blood, in amniotic fluid and in fetal cord blood.

OBJECTIVE: The use of antidepressant drugs during pregnancy is rapidly increasing both in Europe and in the USA, with controversial data regarding side-effects on fetus and newborn. We investigated, in pregnant women and in fetal biological fluids whether the concentrations of a brain protein, Activin A, changed in association with the use of selective serotonin re-uptake inhibitors (SSRI). METHODS: We conducted a case control study in 24 women treated with SSRIs, matched with 24 healthy pregnancies as controls. Maternal blood (during labor, T1), fetal blood (venous (T2) and arterial [T3] umbilical cord blood) and amniotic fluid (T4) were drawn for standard laboratory assessment and for Activin A measurement. RESULTS: Activin A concentrations in maternal and fetal biological fluids were significantly higher in SSRI users than in the control groups(P < 0.05, for all). CONCLUSIONS: Activin A in maternal and fetal biological fluids is increased after SSRI administration in the third trimester of pregnancy. The present findings open up a new cue for further studies aimed at investigating protein's key role in central nervous system protection/damage in pregnant women using these drugs.

Severe valproic acid intoxication: case study on the unbound fraction and the applicability of extracorporeal elimination.

Among anticonvulsants, valproic acid (VPA) is cited as the most frequent cause of unintentional and intentional intoxications. Symptoms of VPA intoxication are diverse and are related to VPA plasma concentration. Although total plasma concentrations of less than 450 mg/l produce limited toxicity, severe intoxications (>850 mg/l) can induce coma and are ultimately life threatening. A 32-year-old comatose woman was admitted to the ICU at our hospital; she suffered from hypotension, respiratory depression, hypoglycaemia, sinus bradycardia, hyperammonaemia, metabolic acidosis, and her core body temperature was 33.7 degrees C. The total VPA plasma concentration was 1244 mg/l with an increased unbound fraction of 85%. After we administered multiple doses of activated charcoal, she underwent continuous veno-venous haemofiltration to reduce the plasma VPA concentration. As the total concentration decreased, the unbound fraction also decreased. Within 20 h of admission, the patient made a full recovery. In cases of VPA intoxication, protein-binding saturation and drug characteristics render extracorporeal elimination, an effective technique for eliminating the unbound drug. Its application should be considered, depending on clinical symptoms, VPA concentration (>300 mg/l), albumin concentration and ammonia concentration (>400 micromol/l). The application of this technique should be weighed against its risks. This case illustrates the clinical significance of applying continuous veno-venous haemofiltration in VPA intoxication because of protein-binding saturation, and suggests when extracorporeal elimination should be considered.

Evaluation of available treatment guidelines for the management of lithium intoxication.

Intoxications with lithium carry considerable risk for long-term morbidity and even mortality. Consequently, any patient suspected of lithium intoxication requires immediate and appropriate care. The objectives of this study were to assess the completeness and the applicability of generally available treatment guidelines for the management of patients with a lithium intoxication and, hence, to provide general recommendations for improvement of existing treatment guidelines. Nineteen treatment guidelines originating from 7 different countries were gathered by searching the Internet, online databases, and textbooks and by contacting different poison information centers and university medical centers. A list of items was composed from the retrieved treatment guidelines and a further literature search. Most relevant items were present in the various guidelines. However, in some guidelines, essential information was missing or potentially hazardous information was provided. Clarity, presentation, and applicability of the guidelines, as assessed using parts of the Appraisal of Guidelines Research and Evaluation instrument, were relatively poor. Regular updates of treatment guidelines should be performed to incorporate new essential information. To improve applicability of guidelines, unambiguous key recommendations, alternative treatments, and special care requirements should be provided and authors are recommended to test treatment guidelines using a panel of less experienced caregivers in a hypothetical case scenario.

Development of an optimal lidocaine infusion strategy for neonatal seizures.

INTRODUCTION: Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias. MATERIALS AND METHODS: As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined. RESULTS: No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are <9 mg/L. Simulations with the developed pharmacokinetic model indicated a reduction in the infusion duration of lidocaine at 6 mg/kg per hour from 12 to 6 h. Thirdly, the new lidocaine dosing regimen was evaluated. Fifteen neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were <9 mg/L. Again preterm infants showed relatively high lidocaine plasma levels. CONCLUSION: A new lidocaine dosing schedule was developed. This new regimen should have a lower risk of cardiac arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined.

Treatment of symptomatic congenital cytomegalovirus infection with valganciclovir.

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. Some congenitally infected infants will develop sequelae later in life, especially sensorineural hearing loss (SNHL) and mental retardation. There is no generally accepted antiviral therapy for the treatment of symptomatic congenital CMV infections yet. We present a neonate with symptomatic congenital CMV infection, who was treated with intravenous (iv) ganciclovir (GCV) during 18 days and subsequently with oral valganciclovir (VGCV) for 5.5 months, in an attempt to prevent development of SNHL. GCV was given intravenously 10 mg/kg/day in two doses and VGCV doses ranged from 280-850 mg/m2 bidaily (bid). Our experience shows that it is not possible to give a fixed dosing regime for VGCV in neonates and that continuous adaptation of dose is necessary to achieve stable target levels of GCV and to keep the viral load in urine at undetectable level. At 18 months of age no hearing deterioration has occurred. While the current findings are encouraging, the limitations of a single case report with a relatively short follow-up emphasizes the need for further prospective randomized studies to evaluate pharmacokinetics, efficacy and safety of VGCV therapy in neonates with congenital CMV infection.

Drug treatment of fetal tachycardias.

The pharmacological treatment of fetal tachycardia (FT) has been described in various publications. We present a study reviewing the necessity for treatment of FT, the regimens of drugs used in the last two decades and their mode of administration. The absence of reliable predictors of fetal hydrops (FH) has led most centers to initiate treatment as soon as the diagnosis of FT has been established, although a small minority advocate nonintervention. As the primary form of pharmacological intervention, oral maternal transplacental therapy is generally preferred. Digoxin is the most common drug used to treat FT; however, effectiveness remains a point of discussion. After digoxin, sotalol seems to be the most promising agent, specifically in atrial flutter and nonhydropic supraventricular tachycardia (SVT). Flecainide is a very effective drug in the treatment of fetal SVT, although concerns about possible pro-arrhythmic effects have limited its use. Amiodarone has been described favorably, but is frequently excluded due to its poor tolerability. Verapamil is contraindicated as it may increase mortality. Conclusions on other less frequently used drugs cannot be drawn. In severely hydropic fetuses and/or therapy-resistant FT, direct fetal therapy is sometimes initiated. To minimize the number of invasive procedures, fetal intramuscular or intraperitoneal injections that provide a more sustained release are preferred. Based on these data we propose a drug protocol of sotalol 160 mg twice daily orally, increased to a maximum of 480 mg daily. Whenever sinus rhythm is not achieved, the addition of digoxin 0.25 mg three times daily is recommended, increased to a maximum of 0.5 mg three times daily. Only in SVT complicated by FH, either maternal digoxin 1 to 2mg IV in 24 hours, and subsequently 0.5 to 1 mg/day IV, or flecainide 200 to 400 mg/day orally is proposed. Initiating direct fetal therapy may follow failure of transplacental therapy.