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The Cochrane Database of Systematic... Aug 2023Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014.
OBJECTIVES
To assess the effects of pharmacological treatments for GOR in infants and children.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old.
DATA COLLECTION AND ANALYSIS
We used standard methodology expected by Cochrane.
MAIN RESULTS
We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean difference between the two different dosing regimens was 2.3 (95% CI -2 to 6.6), and for the lower-weight group, symptom score MD was 4.6 (95% CI -2.9 to 12). Pantoprazole: pantoprazole may or may not improve symptom scores at 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg pantoprazole in children aged one to five years by week eight, with no difference between 0.3 mg/kg and 1.2 mg/kg dosing (0.3 mg/kg mean -2.4 ± 1.7; 1.2 mg/kg -1.7 ± 1.2: MD 0.7 (95% CI -0.4 to 1.8)) (one study, 60 children; very low-certainty evidence). There were insufficient summary data to assess other medications.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H₂antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).
Topics: Adolescent; Child; Humans; Infant; Infant, Newborn; Esomeprazole; Gastroesophageal Reflux; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Ranitidine
PubMed: 37635269
DOI: 10.1002/14651858.CD008550.pub3 -
Andrology Nov 2020The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied...
BACKGROUND
The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and sperm parameters from patients consulting at infertility clinics, but the conclusions of these reports were contradictory. Only two reports investigated the effects of lansoprazole and omeprazole on sperm motility and found lansoprazole to be deleterious and omeprazole to be neutral for sperm motility. The inconsistency of the PPI effect in the previous reports emphasizes the need for more basic research on human spermatozoa, taking into account the hypothesis that the different PPI drugs may have different effects on sperm physiology.
OBJECTIVES
Do PPIs, which are among the most widely sold drug in the word, impact negatively human sperm capacitation and sperm motility?
MATERIALS AND METHODS
The effects of PPIs on human sperm maturation and motility were analyzed by CASA, flow cytometry, and Western blot.
RESULTS
We tested the impact of 6 different PPIs on human sperm motility and capacitation. We showed that pantoprazole, but not the other PPIs, decreased sperm progressive motility and capacitation-induced sperm hyperactivation. We therefore investigated further the effects of pantoprazole on sperm capacitation, and we observed that it had a significant deleterious effect on the capacitation-induced hyperpolarization of the membrane potential and capacitation-associated protein phosphorylation.
DISCUSSION AND CONCLUSION
Our results indicate that exposure to pantoprazole has an adverse effect on the physiological competence of human spermatozoa. As the capacitation process takes place within the female tract, our results suggest that PPIs intake by the female partner may impair in vivo sperm maturation and possibly fertilization. Moreover, the absence of adverse effect by PPIs on mouse sperm emphasizes the need to develop reprotox assays using human material to better assess the effects of medication intake on sperm physiology.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Fertilization; Humans; Lansoprazole; Male; Membrane Potentials; Middle Aged; Omeprazole; Pantoprazole; Phosphorylation; Proton Pump Inhibitors; Rabeprazole; Retrospective Studies; Semen Analysis; Sperm Capacitation; Sperm Maturation; Sperm Motility; Spermatozoa; Young Adult
PubMed: 32609951
DOI: 10.1111/andr.12855 -
Deutsche Medizinische Wochenschrift... Jul 2003
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abdominal Pain; Anti-Ulcer Agents; Benzimidazoles; Chemical and Drug Induced Liver Injury; Cholangitis; Diagnosis, Differential; Female; Gallstones; Humans; Omeprazole; Pantoprazole; Sulfoxides
PubMed: 12840780
DOI: 10.1055/s-2003-40287 -
Gastroenterology Jan 2020
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Aspirin; Double-Blind Method; Humans; Pantoprazole; Rivaroxaban
PubMed: 31704305
DOI: 10.1053/j.gastro.2019.09.050 -
Acta Medica Portuguesa Apr 2024
Topics: Humans; Pantoprazole; Diabetic Ketoacidosis; Chemical and Drug Induced Liver Injury, Chronic; Proton Pump Inhibitors; Diabetes Mellitus
PubMed: 38631049
DOI: 10.20344/amp.20928 -
Clinical Pharmacology in Drug... Feb 2022Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by... (Randomized Controlled Trial)
Randomized Controlled Trial
Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single-center, open-label, randomized, parallel drug-drug interaction trial in healthy adults (EudraCT No. 2020-001470-30). All participants received a single oral dose of 400-mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole-blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography-tandem mass spectrometry. Primary endpoints were whole-blood hydroxychloroquine areas under the concentration-time curve from 0 to 72 hours (AUC ) and peak concentrations (C ). Unpaired 2-sided t-tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty-four participants (12 per group) were included. Hydroxychloroquine AUC and C did not differ between groups without and with pantoprazole (arithmetic mean; AUC , 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; C , 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.
Topics: Adult; Biological Availability; Chromatography, Liquid; Drug Interactions; Humans; Pantoprazole; Proton Pump Inhibitors
PubMed: 34268908
DOI: 10.1002/cpdd.999 -
African Journal of Paediatric Surgery :... 2022Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2...
CONTEXT
Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2 receptor antagonists.
AIMS
We investigated if similar outcomes are achieved with IV pantoprazole, a proton-pump inhibitor (PPI), including the subgroup of delayed presenters in the South African setting.
SETTINGS AND DESIGN
A 5-year retrospective record review (January 2014-December 2018) compared the rate of metabolic correction in patients with hypertrophic pyloric stenosis at two tertiary centres.
SUBJECTS AND METHODS
One centre routinely administers IV pantoprazole (1 mg/kg daily) preoperatively (PPI group) and the other does not (non-PPI group). Fluid administration, chloride supplementation and post-operative emesis were evaluated.
STATISTICAL ANALYSIS
Spearman's rank correlation coefficient was used to calculate statistical significance for discrete dependent variables. Continuous variables were compared between the groups using the Student t-test. Fisher's exact contingency tables were used to classify categorical data and to assess the significance of outcome between two treatment options. P < 0.05 was considered statistically significant.
RESULTS
Forty-two patients received IV pantoprazole and 24 did not. The mean time of metabolic correction was 8 h shorter in the PPI group (P = 0.067). Total pre-operative chloride administration correlated to the rate of metabolic correction in both cohorts (P < 0.0001). Profound hypochloraemia (chloride <85 mmol/l) was corrected 23 h faster in the PPI group (P < 0.004). Post-operative emesis was noted: 0.45 episodes/patient in the PPI group and 0.75 episodes/patient in the non-PPI group (P = 0.01).
CONCLUSIONS
Pre-operative IV pantoprazole administration showed a faster correction of metabolic derangements, and in profound hypochloraemia, the correction occurred substantially faster in the PPI group. Post-operative emesis was significantly less frequent in the PPI group.
Topics: Humans; Pantoprazole; Pyloric Stenosis, Hypertrophic; Retrospective Studies
PubMed: 34916353
DOI: 10.4103/ajps.AJPS_9_21 -
The American Journal of Gastroenterology Jun 2002
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anaphylaxis; Benzimidazoles; Esophagitis, Peptic; Humans; Male; Omeprazole; Pantoprazole; Recurrence; Sulfoxides
PubMed: 12094902
DOI: 10.1111/j.1572-0241.2002.05760.x -
The American Journal of Gastroenterology Nov 2002
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anaphylaxis; Anti-Ulcer Agents; Benzimidazoles; Enzyme Inhibitors; Humans; Male; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Recurrence; Sulfoxides
PubMed: 12425583
DOI: 10.1111/j.1572-0241.2002.07085.x -
Zeitschrift Fur Gastroenterologie Feb 2011A female patient receiving pantoprazole during a corticosteroid therapy for encephalomyelitis disseminata developed severe acute hepatitis one month after initiation of...
A female patient receiving pantoprazole during a corticosteroid therapy for encephalomyelitis disseminata developed severe acute hepatitis one month after initiation of pantoprazole treatment. Other causes of hepatic dysfunction including viral hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, haemochromatosis or Wilson's disease were excluded. Liver biopsy showed severe hepatic lesions with extensive necroses of the parenchyma. One week after discontinuation of pantoprazole the liver function began to improve and gradually the patient fully recovered. One year earlier the patient had been treated with pantoprazole before and had developed a milder form of hepatitis then. This case argues for an idiosyncratic hepatocellular damage caused by pantoprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Failure, Acute; Middle Aged; Pantoprazole; Proton Pump Inhibitors
PubMed: 21298607
DOI: 10.1055/s-0029-1245613