Establishing a Trigger Tool Based on Global Trigger Tools to Identify Adverse Drug Events in Obstetric Inpatients in China

doi:10.21203/rs.3.rs-2352602/v1

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Research Article

Establishing a Trigger Tool Based on Global Trigger Tools to Identify Adverse Drug Events in Obstetric Inpatients in China

https://doi.org/10.21203/rs.3.rs-2352602/v1

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published 15 Jan, 2024

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Background

To examine the performance of an obstetric trigger tool, compared with the spontaneous reporting system (SRS) and global trigger tools (GTTs), in detecting adverse drug events (ADEs) experienced by obstetric units, and to assess the utility and value of the obstetric trigger tool in identifying ADEs of obstetric inpatients.

Methods

Our obstetric triggers were established on the basis of a literature review, retrospective obstetric ADE investigations, trigger extraction and revision, and expert investigations. We conducted a retrospective study to identity ADEs in 300 obstetric inpatient records at the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital from June 1 to September 30, 2018.

Results

Through two rounds of expert investigation, we established 39 preliminary triggers that comprised four modules (12 laboratory tests, nine medications, 14 symptoms, and four outcomes). Three hundred medical records were reviewed by using the obstetric triggers with 49 cases of ADE detected, and the incidence of ADE was 16.33%. Among the 39 obstetric triggers, 22 triggers were positive (56.41%) and 11 of them detected ADE. The positive predictive value (PPV) was 36.36%, and the number of ADEs/100 patients was 16.33 (95% CI, 4.19–17.81). The ADE detection rate, positive trigger rate, and PPV value for the obstetric triggers were significantly augmented, confirming that the obstetric triggers were more specific and sensitive than SRS and GTT.

Conclusion

The obstetric triggers were proven to be sensitive and specific in the active monitoring of ADE for obstetric inpatients, and this could constitute a reference for ADE detection of obstetric inpatients at medical institutions.

global trigger tools (GTTs)

triggers

obstetric inpatients

adverse drug events (ADEs)

positive predictive value (PPV)

David et al. [1] defined ADE as an injury resulting from medical intervention related to drugs, including non-preventable ADEs (adverse drug reactions [ADR]) and preventable ADEs caused by medication errors (ME) [2]. Among the causes of death in the United States, ADR was the fifth leading cause after heart disease, stroke, cancer, and lung disease[3, 4]. In the United States, annual treatment costs for ADR reached $130 billion [5], and it was estimated that as many as 123,000 patients in France needed to be hospitalized annually due to ADR [6]. Medication errors constitute one of the three main causes of death in the United States, and Martin et al. [7] postulated that medication errors induce an elevation in mortality, although additional attention and reports are still required.

Therefore, how to effectively identify and supervise ADE has become a major concern of scientific research and health management departments. The key to preventing ADE is via detection methods, and SRS and adverse-events medical records review are the currently applied detection methods. Although the two methods allow data analysis of ADEs and provide some significant guidance, they comprise retrospective passive measures that lag behind the diagnosis of ADE [8]. Such limitations make it difficult to determine the actual incidence of ADE and may result in missing reports with respect to hospitalizations or deaths caused by ADE. Since most ADEs are preventable, ADE monitoring and reporting are particularly important [9, 10].

In 2003, the Institute for Healthcare Improvement (IHI) launched the global trigger tool (GTT), an active monitoring tool for medically related adverse events; and revised it in 2009[11]. The GTT detected ADE by cue (trigger), a low-cost and low-technology detection method. A “trigger” was defined by the WHO as “the unknown or unconfirmed possible causal relationship between a drug and an adverse event”[12]. The IHI divided triggers within the GTT into six modules of “nursing,” “medication,” “surgical,” “intensive care (ICU),” “perinatal,” and “emergency.” Different trigger modules could then be selected for various adverse events, and of these, the “medication” module encompassed 13 items. Triggers could be used to purposely locate ADE-related content, thus improving the efficiency and accuracy of case reviews[13]. Both Chinese and international studies have confirmed the accuracy and effectiveness of GTT for ADE monitoring [14–17]. However, studies on special populations are rare, and these principally focus on elderly, pediatric, cancer, and ICU inpatients; with no obstetric inpatient analysis in this area of study [18–20].

Female sex is a known risk factor for ADE. Women exhibit nearly twice the risk of having ADE in comparison with men, and are more likely to be hospitalized for ADE [21]. Reasons for this phenomenon remain unclear, but its manifestation could reflect sex-related pharmacokinetic, immunologic, and hormonal factors, and differences in drug use compared with males [22]. Due to significant changes in the pharmacokinetic characteristics of pregnant patients and the differing degrees to which a fetus may be harmed by some drugs passing through the placental barrier, there remain significant differences between pregnant patients and general patients in terms of drug efficacy and safety, and this requires greater attention [23–28].

In 2016, the International Network for Rational Use of Drugs (INRUD)/China Center Clinical Safety Medication Group obtained a total of 84 medication errors that involved pregnant and lactating patients, accounting for 1.27% of the 6,624 reported medication errors nationwide[29]. Due to the low efficiency of current reporting methods and the few information-reporting members of INRUD China (particularly for women’s and children’s specialty hospitals), the number of reported medication errors was relatively small. As a result, ADEs for obstetric patients were likely underestimated. In this study we established a novel high-efficiency trigger tool based on the GTT which can be implemented to detect ADEs in obstetric inpatients retrospectively. Based on detectable results, the trigger tool could then be modified to conform to Chinese obstetric inpatients.

2.1 Literature Search

We conducted a literature search that encompassed studies from January of 1997 to November of 2017 using PubMed and CNKI, and applied the keywords “gestational trigger tool,” “trigger tool,” “gestational,” “obstetric,” “trigger tool,” “obstetrics,” and “pregnancy.” Our inclusion criteria were (1) trigger entries that were specific; (2) the application of triggers in obstetric patients with ADEs; and (3) detection results that were included. After reading abstracts and results of our searches, we noted that there were no investigations of the application of GTTs in obstetric inpatients, and therefore triggers applied to adult inpatients were included.

2.2 Trigger Extraction and Revision

Preliminary triggers were extracted from the included literature. After that, based on obstetric guidelines, ADEs of obstetric patients reported in the Chinese National Adverse Drug Reaction Monitoring System (NADRMS), the common ADEs of drugs used for special diseases of obstetric patients, and the Williams Handbook of Obstetrics, our results were reviewed by a review panel comprising pharmacists and physicians.

2.3 Delphi Experts Investigation

The Delphi method was used to conduct expert surveys in the present study. Based on the informed and voluntary principle, obstetric and neonatological physicians and pharmacists were randomly selected from national medical institutions, and the initial triggers were modified by expert advice that included the rationale and interpretation of entry settings. After several rounds of revisions, triggers showing high consistency among experts were retained.

2.4 Retrospective Records Review

The study was conducted with the approval of the ethical review committee of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital. A total of 300 discharged medical records from the same hospital in the third quarter of 2018 were randomly selected. The inclusion criteria were (1) discharged medical records from July 1, 2018 to September 30, 2018; (2) hospitalized obstetric patients at a gestational age of ≥ 28 w; (3) a patient age of 16–65 years; and (4) a hospitalization duration of > 48 h. Exclusion criteria were (1) a lack of medication used for treatment; and (2) where the primary data of the inpatient medical record were missing.

Our review panel was established according to the IHI white paper. Two junior pharmacists reviewed the records regarding the foundation of the established obstetric triggers, and then a pharmacist or physician at a senior professional post was responsible for reviewing the results of the primary examiner's medical records. Based upon the records, the panel determined whether there was a positive trigger and whether any ADEs occurred. ADE causality was judged using WHO-UMC standards, i.e., including certain, probable/likely, possible, unlikely, conditional/unclassified, and inaccessible/unclassifiable. In accordance with CTCAE5.0, the severity of the ADE injury was divided into five levels.

The causality determination and severity classification were compared with the GTT and SRS to analyze and verify the effectiveness of the established obstetric triggers, and the triggers were then revised on the basis of review results.

Sensitivity of the triggers was judged through adverse events per 100 admissions, adverse events per 1,000 patient days, and ADE detection rate; while specificity was evaluated by trigger PPV (ADE detection frequency/trigger-positive trigger frequency). We analyzed our data using Excel 2010 and SPSS 22.0.

3.1 Trigger Extraction and Revision

We included 27 [4][6–8][14–16][30–49] articles based on our inclusion criteria, and 17 of these entailed the 13 triggers recommended in the white paper. Forty-one triggers were extracted from the articles, the white paper, the characteristics of physiologic changes during pregnancy, the common ADEs of drugs used for specific diseases in obstetric patients, the Williams Handbook of Obstetrics[50], the obstetric guidelines, and a study of ADEs of obstetric patients[51]. Thirty-nine triggers (Table 1) were then ultimately established through two rounds of expert surveys via the 41 trigger modifications, and we included four modules: 12 laboratory examination triggers, nine medication triggers, 14 symptom triggers, and four outcome triggers.

3.2 Patient characteristics

According to the inclusion and exclusion criteria, 300 effective cases were randomly selected, with an average age of 27.45 years and an age range from 18 to 43 years. The length of hospitalization stay was two to 10 days, with an average of 4.34 days. The 300 effective cases comprised 115 cases of cesarean section, 162 cases of delivery, and 23 cases of fetal preservation (eight cases of threatened premature delivery, 11 cases of gestational cholestasis, three cases of fetal growth restriction, and one case of abnormal liver enzymes during gestation).

3.3 Triggers

We reviewed 300 medical records using the 39 obstetric triggers. Of these, 22 triggers were positive (56.41%), and 11 of these detected ADE. A total of 49 ADEs were reviewed, with one (0.33%) that did not trigger all trigger entries during the review process. Among the 300 obstetric inpatients, 120 had positive triggers with a positive rate of 40.00%; and 154 triggers were detected as positive, with an average of 1.28 triggers per patient. The ADE detection frequency was 56 cases and the PPV was 36.36%. The ratio of ADEs/100 patients was 16.33 (95% CI, 4.19–17.81), and ADEs/1,000 patients*days was 36.89 (96% CI, 32.72–41.07). The trigger monitoring results are shown in Table 1.

Table 1

Triggers and PPV
Modules	No.	Triggers	Interpretation	Positive triggers	ADEs	PPV*(95%CI),%
Laboratory tests	L1	K < 3.3 mmol·L^− 1	hypokalemic drugs used	1	0	0.00%
	L2	K > 5.5 mmol·L^− 1	hyperkalemic drugs used	0	0	-
	L3	Mg > 3.5 mmol·L^− 1	hypermagnesemia drugs used	0	0	-
	L4	Na < 130 mmol·L^− 1	hyponatremic drugs used	0	0	-
	L5	Non-diabetic patients: BG < 3.3 mmol/L Diabetic patients receiving hypoglycemic therapy: BG < 3.9 mmol/L	hypoglycemic drugs used inappropriately	17	0	0.00%
	L6	Patients receiving hypoglycemic therapy: FBG > 5.3 mmol/L, 1 h PBG > 7.8 mmol/L, 2 h PBG > 6.7 mmol/L Non-diabetic patients: FBG ≥ 6.1 mmol/L, PBG ≥ 7.8 mmol	hyperglycemic medications used inappropriately	4	0	0.00%
	L7	SCr increased ≥ .3 mg/dL within 48 h or SCr increased to ≧ 1.5 times of baseline within seven days or urine volume < 0.5 mL/(kg·h) & duration > 6 h	nephrotoxic drugs used	0	0	-
	L8	PT > 13 S; APTT > 35 s; INR ≥ 1.5; combined with bleeding symptoms	heparin used excessively	0	0	-
	L9	Platelets < 50×10⁹ /L (excluding physiologic changes and reductions caused by comorbid diseases)	thrombocytopenia drugs used	3	0	0.00%
	L10	①Hyperthyroidism: TSH decreases, TT4 and FT4 increase; ②Hypothyroidism TSH > 4.0 mIU/L or TPOAb + and TSH 2.5–4.0 mIU/L; Excluding combined thyroid disease	antithyroid drugs/hyperthyroidism drugs used	1	0	0.00%
	L11	WBC Ct < 5.9×10⁹/L; neutrophil count < 3900/Ul (excluding decreases caused by disease changes)	leukopenia drugs used	2	1	50.00%
	L12	ALT ≥ 3ULN&R ≥ 5, ALP ≥ 2ULN&R ≤ 2, ALT ≥ 3ULN, ALP ≥ 2ULN&2 < R < 5, R=(ALT measured value/ALTULN)/(ALP measured value/ALPULN)	hepatotoxic drugs used	7	0	0.00%
Medications	M1	protamine given	after heparin administration	0	0	-
	M2	Use of glucocorticoids/antihistamines/calcium gluconate	after drug allergy or anaphylaxis/anaphylactic shock caused by transfusion	1	1	100.00%
	M3	Use of adrenaline	anaphylactic shock	0	0	-
	M4	50% glucose injection (neonates 10%) administered	after drug-induced severe hypoglycemia	0	0	-
	M5	narcan (naloxone)/nalmefene	after opioid poisoning	0	0	-
	M6	laxative or stool softener given	after drug-induced constipation	36	2	5.56%
	M7	Use of live intestinal bacteria preparations/antidiarrheal agents such as montmorillonite	after drug-induced diarrhea	0	0	-
	M8	Use of antiemetics (excluding nausea of pregnancy)	after drug-induced vomiting	1	1	100.00%
	M9	Intravenous injection of calcium gluconate	after magnesium sulfate administration	15	0	0.00%
Symptoms	S1	Skin allergic reaction	after antibiotics/drugs that cause skin reactions administration	3	2	66.67%
	S2	Hypotension/falls	after antihypertensive drugs, sedative hypnotics, and other drug administration	10	6	60.00%
	S3	Elevated blood pressure: higher than systolic blood pressure of 140 mmHg and/or diastolic blood pressure of 90 mmHg (excluding poorly controlled hypertension)	after hypertensive drugs, prostaglandin drugs, ergonovine administration	11	11	100.00%
	S4	Bleeding (including nasal bleeding, gum bleeding, gastrointestinal bleeding, skin purpura)	after drug-induced bleeding (e.g., aspirin)	0	0	-
	S5	Weak contractions, postpartum hemorrhage	after sedatives, analgesics, magnesium sulfate administration	4	3	75.00%
	S6	Excessive uterine contractions, uterine rupture	after oxytocin, prostaglandins, ergonovine administration	7	5	71.43%
	S7	Acral edema, facial edema, periorbital edema, pulmonary edema (the edema is not caused by the original disease)	after hormones, analgesics, NSAIDS, ergonovine administration	0	0	-
	S8	Thromboembolic events (DVT or PE) (excluding spontaneous embolism caused by pregnancy)	①after drugs that may cause thromboembolism ②Insufficient use of anticoagulant drugs	0	0	-
	S9	Basal body temperature rise ≥ 2°C, high fever, chills (excluding stress and infection factors)	Using drugs that increase body temperature and chills	0	0	-
	S10	Nervous system symptoms (dizziness, headache, facial or extremity numbness, lethargy, and fatigue)	after oxytocin, prostaglandins, antibiotic drugs administration	2	2	100.00%
	S11	Gastrointestinal discomfort such as nausea and vomiting (excluding morning sickness during pregnancy)	after drugs causing adverse gastrointestinal reactions	9	9	100.00%
	S12	Vaginal discomfort (burning sensation, pain, and local bleeding) (excluding vaginal discomfort caused by diseases such as vaginitis)	after topical vaginal medication administration	0	0	-
	S13	Heart rate higher than 140 beats/min, arrhythmia	after oxytocin, prostaglandins, ergonovine administration	4	4	100.00%
	S14	Oligohydramnios or oligohydramnios (premature rupture of membranes excluded)	after oxytocin, prostaglandins, ergonovine administration	0	0	-
Outcome	O1	admission to ICU /rescue	ADE-induced serious illness	2	2	100.00%
	O2	Abrupt cessation of medication (long-term use of anticoagulants, antihypertensives, hypolipidemic, hypoglycemic or hormones)	ADE caused withdrawal or ADE appeared due to withdrawal	3	0	0.00%
	O3	Neonatal asphyxia, fetal distress, premature delivery, and neonatal respiratory depression (excluding neonatal umbilical cord torsion and other diseases)	Use of drugs that adversely affect newborns (analgesics, oxytocin, prostaglandins, and ergonovine)	11	7	63.64%
	O4	Neonatal withdrawal symptoms (neonatal hypoglycemia, hypotension, neonatal bleeding, bradycardia, neonatal abnormal muscle movement, lethargy, severe breathing difficulties, and feeding difficulties	Use of drugs that adversely affect newborns (analgesics, oxytocin, prostaglandins, and ergonovine)	0	0	-
Abbreviations: BG = blood glucose, FBG = fasting blood glucose, PBG = postprandial blood glucose, SCr = serum creatinine, PT = prothrombin time, APTT = activated partial thromboplastin time, INR = international normalized ratio, TSH = thyroid stimulating hormone, WBC = white blood cells, NC = neutrophil count, ALT = alanine aminotransferase, ALP = alkaline phosphatase. * PPV = ADEs/positive triggers. - none

Forty-eight ADE cases were detected by the established obstetric triggers and the detection rate of ADE was 97.96%. Nine ADEs were detected by 13 triggers recommended in the white paper, with a detection rate of 18.37%. During the same period, seven ADE cases were reported in the SRS, and the ADE detection rate was 14.29%. The comparison results of the three methods are shown in Table 2.

Table 2

ADE detection status among the three methods
Method	Obstetric Triggers		SRS		GTT		Total
	Positive trigger	No positive trigger	Report	Not reported	Positive trigger	No positive trigger
ADE detection Number	48	1	7	42	9	40	49
ADE detection rate (95% CI)	97.96% (86.87–109.05%)	2.04% (1.81–2.27%)	14.29% (13.60–14.98%)	85.71% (81.57–89.85%)	18.37% (16.29–20.45%)	81.63% (72.39–90.87%)	100%
ADE occurrences per 100 patients	16 (14.19–17.81)	0.33 (0.30–0.37)	0.43 (0.41–0.45)	2.55 (2.43–2.67)	3 (2.66–3.34)	13.33 (11.82–14.84)	16.33 (14.49–18.18)
ADE occurrences per 1000 patient days	36.89 (32.72–41.07)	0.77 (0.68–0.86)	0.79 (0.75–0.83)	4.75 (4.52–4.98)	6.92 (6.14–7.70)	30.75 (27.27–34.23)	37.66 (33.40–41.93)

As shown in Table 3, five triggers of the GTT were positive, with a rate of 38.46%. Thirty-one of the 300 obstetric inpatients had positive triggers, with a positive rate of 10.33%. Of these, 31 triggers were detected as positive, with an average of one trigger per patient. Ten ADEs were detected and the PPV was 32.26%.

Table 3

Trigger conditions for the GTT
No.	Screening index	Positive trigger frequency	ADE detection frequency	PPV
M4	BG < 2.8 mmol/L	17	0	0.00%
M7	Diphenhydramine (Benadryl)Administration	1	1	100.00%
M10	Anti-Emetic Administration	1	1	100.00%
M11	Over-Sedation/Hypotension	10	6	60.00%
M12	Abrupt Medication Stop	2	2	100.00%
Total		31	10	32.26%

Compared with the SRS and the GTT, the ADE detection rate, positive trigger rate, and PPV value were significantly elevated, confirming the specificity and sensitivity of the obstetric triggers.

3.4 Characteristics of ADEs

Forty-nine cases of ADE were detected, with an incidence of 16.33%. The detected ADEs contained 10 categories that primarily involved the cardiovascular system (17 cases, 34.69%), gastrointestinal system (12 cases, 24.49%), female reproductive system (eight cases, 16.33%), and the fetus (seven cases, 14.29%).

There were 15 types of drugs involved, and the top three were reproductive system medications (31 cases, 52.54%), electrolyte drugs (magnesium sulfate injection primarily) (10 cases, 16.95%), and central nervous system drugs (10 cases, 16.95%).

According to the CTCAE5.0, 17 cases of ADEs were classified as grade 1 (17/49, 34.6%), 27 cases as grade 2, (27/49, 55.10%), and five cases as level 3, (5/49, 10.20%); we uncovered no level 4 or level 5 severity.

3.5 Risk factors

Our logistic regression analysis (Table 4) showed that age, hospitalization duration (days), number of drugs administered, and whether cesarean section was performed or whether the women underwent normal delivery were not statistically significant (P > 0.05). The number of antibacterial drugs was statistically significant, but the regression coefficient β was negative, implying protection against ADEs; this was contrary to the previous literature reports that antimicrobial medication was a risk factor for ADEs [6]. The reasons for this apparent paradox may relate to insufficient sample size and certain correlations existing between various risk factors. Thus, sample size needs to be further expanded in future analyses, and other risk factors should be considered.

Table 4

Logistic regression results of risk factors for the occurrence of ADE.
Factor	OR (95% CI)	P value
Age	1.059 (0.985–1.138)	0.123
Length of hospital stay	1.153 (0.869–1.3529)	0.324
Number of drugs	1.093 (0.848–1.409)	0.493
Number of antibacterial drugs	0.273 (0.094–0.792)	0.017
Number of injection drugs	0.816 (0.511–1.303)	0.394
Cesarean section	1.181 (0.399–3.501)	0.764
Normal delivery	0.520 (0.082–3.294)	0.487

4.1 Sample size

We randomly selected 300 medical records for this analysis and averaged 50 copies every two weeks, which was higher than the sample size recommended by the white paper. The Mevik[52]study showed that increasing the sample size produced no significant effect on the type and severity of ADE detection, but that it could increase the detection rate of ADE. The ADE detection rate in the present study was 36.89 ADEs/1000 patient days, and this approximated the rate of 39.3 ADEs/1000 patient days in the Mevik[52]study where 70 samples were drawn every two weeks (totaling 1680). However, the sample size in our study required further expansion to analyze the risk factors for obstetric inpatient ADEs and to improve the ADE detection rate.

4.2 ADE detection

A total of 48 ADEs were detected by the established obstetric triggers, and the incidence of ADE was similar to that observed from the literature (10–20%). A majority of the ADEs were mild-to-moderate injuries—accounting for 89.8%—but we noted no ADEs that caused permanent injuries or deaths, and this may be related to insufficient sample size. Most of the detected ADEs were related to issues within the cardiovascular system, gastrointestinal system, and female reproductive system—accounting for 34.69%, 24.49%, and 16.33%, respectively. The cardiovascular system injuries were specifically manifested as elevated blood pressure and hypotension. Blood pressures that exceeded 140/90 mm Hg were primarily due to the use of oxytocin and ergonovine, while hypotension was caused by magnesium sulfate. Application of prostaglandin drugs led to nausea, vomiting, diarrhea, or other gastrointestinal disturbances and excessive uterine shrinkage. This ADE-detection result was consistent with the clinical medication characteristics of obstetric inpatients and a study on the occurrence of ADRs in local obstetric patients. By observing doctors and nurses in the operating room, we ascertained that some ADEs were not recorded when the clinical manifestations were mild and when special treatment was not required. We therefore posit that it is necessary to enhance the ability of medical staff to identify and summarize the common ADEs in obstetrics.

4.3 Validity of triggers

Forty-eight cases of adverse reactions were detected based on the established obstetric triggers, while only seven cases were reported by the SRS during the same period, demonstrating that the obstetric triggers, in comparison with SRS, showed superior monitoring performance. This result was consistent with the conclusions reached by Classen et al. [4] that revealed that “the detection rate of ADE by trigger tool was about 10 times higher than the previous two methods (SRS and patient safety indicator monitoring).” Through two rounds of the Delphi method in the current study, the established obstetric triggers manifested a PPV of 36.36%, which was more sensitive and specific than either SRS or GTT. The effectiveness of the obstetric triggers was therefore verified. However, 17 of the 39 triggers were not triggered, with a negative rate of 43.59%. Thus, according to the low positive trigger rate of some triggers, further revision is required.

4.4 Revision of the triggers

A new round of trigger revisions was executed based on the results of the medical records review.

Revision of untriggered trigger entries

With respect to the untriggered items, M1 “protamine given,” S4 “bleeding,” S8 “thromboembolic events,” and S14 “oligohydramnios or oligohydramnios” were not triggered. Four entries (M1, S4, S8, and S14) were deleted in accordance with a drug used during the perinatal period and its trigger probability.

Revision of triggers reflecting a low PPV

To improve the accuracy of the triggers, we conducted revisions on the triggers with a low PPV. During the review of the medical records, we found that the trigger “intravenous injection of calcium gluconate” was triggered 15 times (principally in patients with eclampsia or pre-eclampsia), but that no ADE was noted. Studies have shown that Ca^+ 2 stimulated neuromuscular excitement and promoted blood coagulation, and the intravenous injection of calcium gluconate before cesarean section reduced the amount of oxytocin, intraoperative and postoperative bleeding, and effectively prevented postpartum hemorrhage [53,54]. The condition of this trigger entry should therefore be defined as “intravenous injection of calcium gluconate and Mg > 5 mmol·L^− 1.”

Of the enrolled patients, 115 underwent cesarean section; and those who did not experience flatulence in the two days after the operation received keratin and/or lactulose to improve constipation caused by surgery. As a result, only two ADEs were detected in the 36 triggers of “laxative or stool softener given”; and this was subsequently revised as a trigger in “non-cesarean section patients who used laxatives or stool softeners.”

After verification of overall validity, the revised triggers contained a total of 35 items comprising 12 laboratory tests, eight medications, 11 symptoms, and four outcomes.

There were some limitations to the present study. First, in this study we relied on the judgment of the examiner to determine whether ADE occurred. Although the study team was trained via a medical record review of the IHI white paper, the prevalence of ADE may still have been underestimated due to a lack of actual clinical training and experience in the substantial information review. Second, the examiner's classification of ADE severity was subjective, especially with respect to some temporary injuries; and the examiner may have exaggerated the severity of the ADE. Third, the study was conducted in a specialist hospital, and the composition of patients and medication habits therefore likely restricted the positive activation of the triggers. This might create certain limitations when adopted by other medical institutions, and appropriate modifications would therefore need to be undertaken according to each specific situation.

In this study, 17 triggers remained untriggered, which may relate to insufficient sample size, the composition of obstetric inpatients, and the characteristics of the clinical medications. The PPV for five triggers was 100%, and the trigger frequency fluctuated between a minimum of one occurrence and a maximum of 11. The PPV obtained may thus also be biased due to insufficient sample size.

The review time for each medical record as recommended in the IHI white paper was 20 minutes. However, when some medical records were complicated due to comorbidities or a long hospital stay, the review time needed to be extended, potentially uncovering additional ADEs in these specific medical records.

The obstetric triggers established in this study were reasonable and were proven to be sensitive and specific in the active monitoring of ADE in obstetric inpatients. Compared with SRS and GTT, ADE was accurately detected by the obstetric triggers, showed significant advantages; and provided a reference for ADE monitoring of obstetric inpatients in medical institutions.

Contribution to the Field Statement

We herein applied the GTT to monitor ADE in obstetric inpatients for the first time in China and internationally. By investigating the occurrence of ADR in pregnant patients in Sichuan Province, the characteristics of ADR during pregnancy were comprehensively summarized, laying the foundation for an improvement in the local suitability of triggers. According to the physiologic characteristics of pregnant patients and specific obstetric drugs administered, triggers were then revised appropriately. We considered ADEs for the female reproductive system, fetus, and newborn, and established unique obstetric triggers. We postulated that the obstetric triggers were more suitable for the practical application of inpatients in a local department, and that the triggers could predict the occurrence of ADE more efficiently and accurately than other methods.

Ethics approval and consent to participate

The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital. Written informed consent was obtained from individual or guardian participants.

Consent for publication

Not applicable

Availability of Data and Materials

All data generated or analysed during this study are included in this published article

Competing Interests

The authors declare that they have no conflicts of interest.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Shan Wu, Qinan Yin, and Yuan Bian; and the first draft of the manuscript was prepared by Shan Wu and Qinan Yin. All authors commented on previous versions of the manuscript, and read and approved the final manuscript. The authors are thankful to their medical and pharmaceutical colleagues for providing meaningful advice on the establishment of the GTT and assisting in the collection of surveys.

Acknowledgements

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Shan Wu and Qinan Yin. The first draft of the manuscript was written by Shan Wu and Qinan Yin. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This study was funded by the National Key Research and Development Program of China (2020YFC2005500) and the Key Research and Development Program of Science and Technology Department of Sichuan Province (2019YFS0514).

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No competing interests reported.

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Editorial decision: Revision requested
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You are reading this latest preprint version

Establishing a Trigger Tool Based on Global Trigger Tools to Identify Adverse Drug Events in Obstetric Inpatients in China

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusion

1 Introduction

2 Methods

2.1 Literature Search

2.2 Trigger Extraction and Revision

2.3 Delphi Experts Investigation

2.4 Retrospective Records Review

3 Results

3.1 Trigger Extraction and Revision

3.2 Patient characteristics

3.3 Triggers

3.4 Characteristics of ADEs

3.5 Risk factors

4 Discussion

4.1 Sample size

4.2 ADE detection

4.3 Validity of triggers

4.4 Revision of the triggers

5 Research Limitations

6 Conclusions

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1