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Life-Threatening Infant Overdose of Sodium Chloride

Hamline M, McGlynn G, Lee A, et al. Life-Threatening Infant Overdose of Sodium Chloride. PSNet [internet]. Rockville (MD): Agency for Healthcare Research and Quality, US Department of Health and Human Services. 2020.


Hamline M, McGlynn G, Lee A, et al. Life-Threatening Infant Overdose of Sodium Chloride. PSNet [internet]. Rockville (MD): Agency for Healthcare Research and Quality, US Department of Health and Human Services. 2020.

Michelle Hamline, MD, PhD, MAS, Georgia McGlynn, RN, MSN-CNL, CPHQ, Andrew Lee, PharmD, and JoAnne Natale, MD, PhD | May 27, 2020
View more articles from the same authors.

The Case 

An infant with trisomy 21 underwent repair of a complete atrioventricular canal defect and was subsequently cared for in the pediatric intensive care unit (PICU). Because of a prolonged low cardiac output state, total parenteral nutrition (TPN) was initiated two days following surgery. For pediatric patients, TPN at this hospital is ordered daily by 12:00 noon in order to allow adequate time for cross-checking the order with both the dietician and pediatric pharmacist, as well as preparing the new solution. Per PICU protocol, infusion of the new TPN solution starts early the following morning.

After several days of TPN, the current TPN ordered by the attending physician expired and was not reordered in time to be mixed for the following day. Since it was a weekend, a dietician was not on staff to flag the missing order. To maintain hydration and provision of calories, at 1:00 am an order was placed for replacement fluid, which should have included a standardized dextrose concentration of 20%, with additives of sodium chloride 7.7 mEq/100 mL, potassium chloride 2 mEq/100 mL, and calcium gluconate 100 mg/100 mL. The dextrose, potassium chloride, and calcium gluconate orders were entered correctly. However, the free-text order concentration for sodium chloride was mistakenly entered as 77 mEq/100 mL, a ten-fold higher concentration than intended. The solution was verified and mixed by the overnight non-pediatric pharmacist, who was unaccustomed to working night shift and busy orienting a new pharmacist at the time. The custom intravenous fluid was verified and administered by the baby’s PICU nurse.

After this fluid had been infusing for 16 hours, the PICU physician noted the error in the intravenous fluid order, discontinued the fluids, and ordered replacement fluids. Laboratory tests obtained at that time showed the patient’s serum sodium at 188 mEq/L (normal range 133-142 mEq/L) and chloride at 166 mEq/L (normal range 95-110 mEq/L). The attending PICU physician who placed the incorrect fluid order met with the patient’s family, expressed regret for the error, discussed the immediate effects and the next steps in the care of their baby, and addressed their questions. The patient’s sodium and chloride levels were slowly and safely corrected to normal range. The patient’s mental status remained at baseline. The infant’s family and attending physician met regularly for discussions and reconciliation. 

The Commentary 

By Michelle Hamline, MD, PhD, MAS, Georgia McGlynn, RN, MSN-CNL, CPHQ, Andrew Lee, PharmD, and JoAnne Natale, MD, PhD

Background and Significance 

Adverse drug events (ADEs) are estimated to impact up to 19 percent of hospital inpatients within the Western world1 and can prolong length of stay, increase mortality, and contribute to rising healthcare costs.2,3 Preventable ADEs, referring to the subset of ADEs caused by medication errors, are estimated to account for up to a third of all ADEs.1 While medication errors can occur at any step along the pathway from prescribing to dispensing and administering the medication,4-6 prescribing errors are a particularly common cause of adverse drug events in the inpatient setting.6 Hospital-based prescriber working conditions associated with prescribing errors include overnight shift, high patient load, competing demands, and fatigue.7

Pediatric patients are at especially high risk for medication errors, with some studies finding up to 95 percent of all pediatric intensive care unit (PICU) admissions affected by a medication error in some form.8 Risk factors for medication errors in pediatric patients include the need for individualized weight-based dosing and specialized drug formulations, as well as the relative inexperience of physicians working with children in many clinical settings.9

The Institute for Safe Medication Practices (ISMP) publishes a list of high-alert medications, defined as medications that carry a heightened risk of causing substantial harm when administered in error.10 Both total parenteral nutrition (TPN) and intravenous sodium chloride formulations have been identified as high-alert medications by ISMP, yet there is still frequently a lack of standardization in ordering, verifying, compounding, and administering these medications, making them particularly prone to error.11,12

System Errors Contributing to this Medication Error

A systems approach to medication errors views such errors as “predictable human failings in the context of poorly designed systems.” Four main system errors contributed to the medication error made in the care of this patient. First, the TPN re-ordering process was inconsistent. Second, clinical decision support was not built-in for the ordering of custom intravenous fluids. Third, staffing was limited and lacked availability of a pediatric pharmacist overnight or a consistent dietician on weekend rounds. And finally, a standardized method of communicating patient safety concerns was apparently not in place.

Inconsistent TPN re-ordering process 

In this case, TPN was required to be re-ordered daily for pediatric patients by 12:00 noon. This pre-specified order deadline allows for sufficient time for verification and mixing of the new TPN solution. This requirement aligns with prior Best Practice recommendations that emphasize the importance of time-limited TPN orders to allow for frequent patient re-evaluation and advise that such orders “be prescribed and transmitted when supported by properly trained personnel who regularly perform this task...usually during daytime hours.”13 However, in this situation, there was no alert to notify physicians, nurses, or pharmacists that the patient’s current TPN was set to expire, nor that a new bag of TPN had not been ordered. Rather, the safety process often relied on a dietician to notify the team if the TPN had not been ordered, but this process was inconsistent due to limited dietician staffing on the weekends, when this event occurred. 

Lack of clinical decision support for custom intravenous fluids 

Because the TPN had not been ordered in time, a substitute bag of intravenous fluid with appropriate dextrose and electrolyte concentrations was needed to maintain hydration and provide calories until a new TPN solution could be infused on the following day. These replacement intravenous fluids were ordered using a pre-existing order set in which electrolyte additives may be entered as free-text and are ordered in mEq/100 mL. However, pediatric intensivists are accustomed to utilizing concentrations of mEq/L in intravenous fluid and TPN orders. This difference in units used to describe the concentration of electrolytes, and absence of clinical decision support, almost certainly contributed to the error described.

Limited pharmacy and dietician staffing 

As previously noted, a pediatric dietician was not available on the weekend day that this event occurred. At this hospital, dieticians were often relied upon to notify the rest of the team if a patient’s TPN had not been appropriately ordered for the day. However, without a dietician available, this notification did not happen, which necessitated the ordering of replacement custom intravenous fluids.

Best practice dictates that, when a new order for custom intravenous fluid is received, the pharmacy technician draws each additive into a syringe, which is then checked by a pharmacist before it is mixed into the bag of intravenous fluid. The final product is then checked again by the pharmacist, thus completing a system of checks and balances that often helps to prevent errors. For this patient, both the pharmacy technician and the pharmacist must have verified the additives as ordered, as well as the final product, but without noticing the concentration error. Of note, four vials of sodium chloride would have been necessary to make the bag of intravenous fluid, which should have been noticed as irregular for custom intravenous fluids by the pharmacist and the pharmacy technician.

In this case, the night shift pharmacist was not specialty-trained as a pediatric pharmacist and such a fluid order would be uncommon in adult medicine. The pharmacist’s lack of familiarity with standard procedures for filling orders for PICU patients, and his/her simultaneous responsibility for orienting a new pharmacist, may have contributed to missing the ordering error. In other words, human factors were involved in the cognitive error of not recognizing the irregularity of adding four vials of sodium chloride into the bag of custom intravenous fluid.

Absence of standardized patient safety communication  

It is unclear, based on the Case description, whether the patient’s nurse or another care team member noted the absence of a new TPN order or the excessively high sodium chloride concentration when verifying the custom intravenous fluid for administration. It is also not clear from the Case description whether any standardized process of communicating such patient safety concerns amongst the patient care team members or with leadership was in place, even if other team members had noted a concern. Such measures are critical to promoting a culture of safety, both within the care team and at the organizational level.

Systems Change Needed/Quality Improvement Approach 

Streamlined TPN re-ordering process 

The American Society for Parenteral and Enteral Nutrition has published a set of best practice guidelines for the prescribing of TPN, advising that processes for TPN management should be standardized.13 Many of the TPN management processes described in this Case were already standardized based on these recommendations, including time-limiting orders to allow for frequent patient reassessment and maximizing use of daytime resources for TPN preparation. However, the TPN error in this Case revealed the need for a more effective safety net to prevent expiration of TPN orders without new orders in place.  

In response to this error, improved processes which incorporate end-user input and feedback should be implemented for TPN re-ordering. This could include additional electronic health record (EHR) alerts to the pharmacist and/or physician that indicate whether a new bag of TPN has been ordered for the following day. For example, the pharmacist’s EHR view could contain an alert for all patients for whom there is a current TPN order, notifying the pharmacist if an order for TPN for the following day is or is not present. Such a system could be applied for both adult and pediatric patients.

Built-in clinical decision support for ordering custom intravenous fluids 

The medication error in this Case also reveals the need to standardize the ordering of all custom intravenous fluids in a manner similar to ordering TPN. While studies have demonstrated a key role for computerized provider order entry (CPOE) in reducing medication errors, there is wide variability in the effectiveness of CPOE depending on its level of sophistication.14 As CPOE has evolved, the addition of clinical decision support systems has enhanced patient safety and reduced medication errors across clinical settings.15,16

To avoid errors such as the one described in this Case, intravenous fluid order sets should be standardized to provide integrated clinical decision support with respect to overall volume and additives. For example, intravenous fluid order sets should be standardized to include a uniform bag size of 250 mL for patients who weigh less than or equal to 10 kg and 500 mL for patients who weigh greater than 10 kg. Also, several “quick pick” options for making substitutions can be implemented for various appropriate electrolyte concentrations, with the total electrolyte composition auto-calculated within the EHR, and free text can be eliminated. Prescribing alerts should also be considered for electrolyte concentrations exceeding pre-set limits, such as dextrose exceeding 25%, sodium exceeding 0.90%, potassium exceeding 20 mEq/L, calcium exceeding 8 mEq/L, and heparin exceeding 1 unit/mL.

Expanded pharmacy and dietician staffing 

Several published studies have shown that clinical pharmacists play a key role in preventing medication-related errors. Clinical pharmacists may obtain important additional history from the patient (e.g., their medications and allergies), catch errors in prescribing, suggest medication changes, and ensure adequate patient monitoring.6,17 In these ways, pharmacists serve an important protective function in the “swiss cheese” model to help ensure patient safety.18 Notably, increased pharmacist workload has been associated with a higher rate of dispensing errors, whereas lower pharmacy workload is associated with an increase in prescription-related suggestions.19 Thus, adequate pharmacist staffing, for both day and night shifts, is critical to help prevent medication errors such as the one described in this Case. Additional pediatric training for all night-shift pharmacists may also help promote recognition of similar types of prescribing errors in the future.

Similarly, given the dietician’s role in alerting the care team to the expiration of TPN orders, appropriate dietician staffing is fundamental to preventing similar errors in the future. While many published studies have not focused on the role dieticians play in preventing nutrition-related errors in hospitalized patients, previous work has shown that better nutritional delivery improves pediatric critical care outcomes, suggesting an important role for dieticians in the care of this patient population.20

Standardized methods of patient safety communication

The Institute for Healthcare Improvement (IHI) has developed a toolkit of Patient Safety Essentials designed to improve teamwork and communication with the goals of understanding and preventing errors and creating more reliable healthcare systems.21 It is unclear in this Case whether other team members noticed the omission of a new TPN order or the inappropriate sodium chloride concentration in the new custom intravenous fluids. For team members who notice such errors, the IHI tools provide a standardized method of communicating their concerns with the rest of the care team and with clinical leadership. Examples of tools in the toolkit include: the daily Safety Huddles Tool,22 weekly Patient Safety Leadership WalkRounds,23 and the Safety Briefings Tool.24 Implementation of these practices have been shown to increase patient safety awareness, improve the identification of patient safety issues, and reduce time to resolution of such issues.25-29 Similar measures could be implemented at the hospital where the event described in this Case occurred to help prevent errors like it from reaching the patient.

Loop Closure

Implementation of built-in clinical decision support systems, adequate pharmacy and dietician support, and standardized methods of patient safety communication will require a longitudinal multidisciplinary effort with strong administrative buy-in. Success can be ensured through the application of quality improvement methods during implementation and iterative modifications of these system changes. The payoff in patient safety and prevention of future similar errors will certainly be worth the investment.

Take-Home Points 

  • Ordering of TPN and custom intravenous fluids holds high potential for error, particularly in the pediatric population. 
  • Physicians, pharmacists, nurses, and dieticians all have key roles to play in preventing medication-related errors associated with TPN and custom intravenous fluids. 
  • Built-in clinical decision support systems implemented within the electronic health record can help prevent errors associated with standardization of ordering, preparation, and administration of TPN and custom intravenous fluids.
  • Ensuring adequate pharmacy and dietician support is a key factor in preventing human-related errors in the ordering and preparation of TPN and custom intravenous fluids. 
  • Standardized methods for communicating about patient safety, including daily huddles and leadership walk rounds, are critical for establishing a culture of safety and improving recognition and resolution of patient safety events.


Michelle Hamline, MD, PhD, MAS
Assistant Professor of Clinical Pediatrics

Associate Director of Pediatric Quality and Safety

Department of Pediatrics, Division of Pediatric Hospital Medicine

UC Davis Health

Georgia McGlynn, RN, MSN-CNL, CPHQ
Quality Improvement Nurse Analyst

Clinical Affairs Division, Quality and Safety

UC Davis Health

Andrew Lee, PharmD
Pediatric Pharmacist Supervisor

Department of Pharmacy Services

UC Davis Health

JoAnne Natale, MD, PhD
Professor of Clinical Pediatrics

Vice Chair of Pediatric Quality and Safety

Director of Children’s Hospital Quality and Safety

Chief of Staff

Department of Pediatrics, Division of Pediatric Critical Care

UC Davis Health


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This project was funded under contract number 75Q80119C00004 from the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services. The authors are solely responsible for this report’s contents, findings, and conclusions, which do not necessarily represent the views of AHRQ. Readers should not interpret any statement in this report as an official position of AHRQ or of the U.S. Department of Health and Human Services. None of the authors has any affiliation or financial involvement that conflicts with the material presented in this report. View AHRQ Disclaimers

Hamline M, McGlynn G, Lee A, et al. Life-Threatening Infant Overdose of Sodium Chloride. PSNet [internet]. Rockville (MD): Agency for Healthcare Research and Quality, US Department of Health and Human Services. 2020.

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