This study tests the feasibility of a large study of stress ulcer prophylaxis in critically ill children. Children admitted to the Pediatric Intensive Care Unit who are expected to require mechanical ventilation for more than 48 hours will be randomized to intravenous pantoprazole 1 mg/kg or matching placebo once daily until they no longer need mechanical ventilation.

Despite sparse pediatric data on the effectiveness of stress ulcer prophylaxis to prevent gastrointestinal (GI) bleeding, 60% of critically ill children receive these medications. This may have unintended consequences - increasing the risk of nosocomial infections - which may be more serious and common than bleeding these drugs are prescribed to prevent. A large randomized trial (RCT) is needed to assess the balance of these risks and benefits, to determine if a strategy of withholding stress ulcer prophylaxis in critically ill children is not inferior to a strategy of routine stress ulcer prophylaxis. RCTs in pediatric critical care are exceptionally challenging to complete; thus, a rigorous pilot RCT is crucial. The pilot may prevent pursuit of a trial that is ultimately not feasible - which is ethically and financially responsible. It is more likely that this carefully designed pilot trial will ensure that the larger trial we undertake is successful.

Inclusion Criteria:

1. less than 18 years of age
2. >4 months of age
3. requires respiratory support in the form of invasive mechanical ventilation, non-invasive mechanical ventilation, or high-flow oxygen
4. the attending physician expects the child to require respiratory support for at least 2 more days

Exclusion Criteria:

1. histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) use for >1 week in the past month
2. active GI bleeding Blood in the nasogastric (NG) tube or coffee-ground emesis suspected by the attending physician to be from the oropharynx is not an exclusion criterion.
3. documented severe reflux, active H. pylori infection, severe esophagitis, Zollinger Ellison syndrome, Barrett's esophagus, peptic ulcer bleeding within 8 weeks
4. are receiving methylprednisolone 15 mg/kg/day or more (or equivalent) Equivalent doses: methylprednisolone, prednisone or prednisolone 15 mg/kg/day; dexamethasone 3 mg/kg/day; hydrocortisone 60 mg/kg/day
5. are receiving mycophenolate (enteral), methotrexate, nelfinavir, atazanavir, saquinavir, posaconazole
6. chronic ventilation on usual pressure settings and rate
7. nocturnal or intermittent non-invasive ventilation only
8. are eating, nursing, or if chronically fed via feeding tube, receiving usual feeds
9. received more than 1 daily-dose equivalent of acid suppressive medication in the PICU
10. were previously enrolled in this trial
11. are currently enrolled in a potentially confounding trial
12. are known to be pregnant or breastfeeding
13. are known to be allergic to pantoprazole or any other ingredient in the product
14. are not expected to survive this PICU admission because of palliative care or limited life support