Prophylactic Acetaminophen Research Articles

Increased Postoperative Opioid Consumption in the Presence of Coadministration of 5-Hydroxytryptamine Type 3 Antagonists with Acetaminophen: A Hospital Registry Study.

Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied. A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013). A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis.

Comparison of ultrasound-guided erector spinae plane block versus transmuscular quadratus lumborum block for postoperative analgesia after caesarean delivery: A prospective randomized non-inferiority clinical trial.

Regional techniques are a part of multimodal analgesia following cesarean delivery. Cesarean delivery warrants a regional technique, which can provide somatic and visceral analgesia-like quadratus lumborum block (QLB) and erector spinae plane block (ESPB). In this study, we investigated the non-inferiority of ESPB at T12 and transmuscular-QLB (TQLB) at L2-L3 for postoperative analgesia in cesarean delivery. In this prospective, randomized, non-inferiority trial, 124 patients undergoing cesarean delivery were enrolled to receive bilateral TQLB or ESPB with 20 mL of 0.25% ropivacaine on each side. All patients received prophylactic acetaminophen and ketorolac for 2 days. Our primary objective was to compare the total tramadol consumption in the first 48 h between the two groups. Secondary objectives were to compare cumulative tramadol consumption, postoperative Numeric Rating Scale (NRS) score at rest, and with movement at various time points, the time for first rescue analgesic requirement, development of complications related to the block, and patient satisfaction with analgesia between the two groups. The total tramadol consumption in 48 h (47.3 ± 34.9 mg in ESPB and 50.9 ± 38.7 mg in TQLB), duration of first rescue analgesic (22.8 ± 15.8 h in ESPB and 22.7 ± 15.6 h in TQLB), and patient satisfaction were similar between the two groups. Both groups had similar pain scores except at rest at 6 h and on movement at 4 h, 6 h, and 36 h, whereas the ESPB group had lower NRS scores (P < 0.05). The analgesic effect of bilateral ESPB at T12 was non-inferior to that of bilateral TQLB post-caesarean delivery.

Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option. This study evaluated the minimum effective dose of prophylactic acetaminophen to close the ductus and assessed the safety and tolerability profile in extremely preterm infants at 23-26 weeks of gestation. A dose finding trial with Bayesian continual reassessment method was performed in a multicenter study with premature infants hospitalized in neonatal intensive care unit. Infants of 23-26 weeks of gestation and post-natal age ≤ 12 h were enrolled. Four intravenous acetaminophen dose levels were predefined. The primary outcome was the ductus arteriosus closing at two consecutive echocardiographies or at day 7. The main secondary objectives included the safety of acetaminophen on hemodynamics and biological hepatic function. A total of 29 patients were analyzed sequentially for the primary analysis with 20 infants assigned to the first dose level followed by 9 infants to the second dose level. No further dose level increase was necessary. The posterior probabilities of success, estimated from the Bayesian logistic model, were 46.1% [95% probability interval (PI), 24.9-63.9] and 67.6% (95% PI, 51.5-77.9) for dose level 1 and 2, respectively. A closing or closed pattern was observed among 19 patients at the end of treatment [65.5% (95% confidence interval (CI), 45.7-82.0)]. No change in alanine aminotransferase values was observed during treatment. A significant decrease in aspartate aminotransferase values was observed with postnatal age. No change in systolic and diastolic blood pressures was observed during treatment. Minimum effective dose to close the ductus was 25 mg/kg loading dose then 10 mg/kg/6 h for 5 days in extremely preterm infants. Acetaminophen was well tolerated in this study following these doses. ClinicalTrials.gov Identifier: NCT04459117.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis.

Prophylactic Acetaminophen or Ibuprofen Result in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial

Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed.

Effects of Administering Prophylactic Acetaminophen on Short-term Complications of Vaccination in 6-month-old Infants.

Background:We aimed to assess the effects of administering prophylactic acetaminophen on short-term complications of vaccination in 6-month-old infants admitted to a private pediatric clinic in Rasht (Iran) during 2002–2013.Methods:This quasi-experimental study was conducted on 696, infants aged 6-month-old admitted to a pediatric clinic in Rasht before vaccination during 2002–2013. Overall, 31 infants were excluded during the course of the study. While prophylactic acetaminophen was administered in 322 participants (intervention group), 343 infants (control group) received acetaminophen after vaccination. Data were collected by a checklist including complications such as fever, drowsiness, anorexia, seizure, long and excessive crying, mood change, pain, and wound at the site of injection, abscess, induration, limb swelling, and erythema. The time of occurrence of each complication was also recorded. Data were analyzed by Chi-square test in SPSS 16.0. P < 0.05 was considered significant.Results:Six hundred sixty-five participants (49.6% boy) were assessed in this study. The intervention and control groups had no significant difference in terms of sex distribution (P = 0.53). Short-term complications occurred in 45% of the infants. The most common complications were erythema (24.4%), induration (19.9%), and low-grade fever (16.1%). There was a significant relation between administering prophylactic acetaminophen and the incidence of low-grade fever (P = 0.01), induration (P = 0.01), and anorexia (P = 0.03).Conclusions:Our findings indicated the efficacy of prophylactic acetaminophen in reducing postvaccination complications in a population of Iranian infants. According to our findings, further research is required to determine the preferred dose and time of administering acetaminophen.

Infant sleep after immunization: randomized controlled trial of prophylactic acetaminophen.

To determine the effects of acetaminophen and axillary temperature responses on infant sleep duration after immunization. We conducted a prospective, randomized controlled trial to compare the sleep of 70 infants monitored by using ankle actigraphy for 24 hours before and after their first immunization series at ∼2 months of age. Mothers of infants in the control group received standard care instructions from their infants' health care provider, and mothers of infants in the intervention group were provided with predosed acetaminophen and instructed to administer a dose 30 minutes before the scheduled immunization and every 4 hours thereafter, for a total of 5 doses. Infant age and birth weight and immunization factors, such as acetaminophen use and timing of administration, were evaluated for changes in infant sleep times after immunization. Sleep duration in the first 24 hours after immunization was increased, particularly for infants who received their immunizations after 1:30 pm and for those who experienced elevated temperatures in response to the vaccines. Infants who received acetaminophen at or after immunization had smaller increases in sleep duration than did infants who did not. However, acetaminophen use was not a significant predictor of sleep duration when other factors were controlled. If further research confirms the relationship between time of day of vaccine administration, increased sleep duration after immunization, and antibody responses, then our findings suggest that afternoon immunizations should be recommended to facilitate increased sleep in the 24 hours after immunization, regardless of acetaminophen administration.

Infant Sleep After Immunization: Randomized Controlled Trial of Prophylactic Acetaminophen

Infant Sleep After Immunization: Randomized Controlled Trial of Prophylactic Acetaminophen

Immediateversusas-needed acetaminophen for post-immunisation pyrexia

Local and minor systemic adverse events are frequently seen after routine immunisation with diphtheria-pertussis-tetanus. Antipyretics are frequently prescribed for these events and prophylactic administration of acetaminophen is occasionally recommended. To determine whether prophylactic administration of acetaminophen has any effect in reducing the incidence of post-vaccination side-effects. A prospective, comparative trial with telephone interview-based outcome assessment. OPD and immunisation room of a tertiary-care paediatric hospital. 167 children aged between 1·5 and 24 months presenting for routine immunisation were enrolled and allocated to the 'immediate' or 'as-needed' group. The immediate group had received acetaminophen syrup (10-15 mg/kg, single dose) immediately after vaccination (n=89); children in the as-needed group were not given prophylactic acetaminophen (n=78). Parents of both groups were free to give further doses of acetaminophen for fever, pain or irritability. The primary outcome was the incidence of parent-reported fever needing rescue acetaminophen, and the secondary outcome was the incidence of local side-effects. There was a statistically significant higher incidence of fever and irritability in the 1st 6 hours following vaccination in the as-needed group (p=0·04). No difference was observed in the incidence of local and systemic side-effects or the median number of acetaminophen doses required by the children in the two groups. Routine prophylactic acetaminophen after DPT vaccination was effective in reducing the frequency of fever and irritability in the initial 6 hours. However, given that a similar number of doses of acetaminophen was required in both groups, it seems inappropriate to expose all infants receiving DPT vaccination to the possible adverse effects of routine administration of acetaminophen.

Prophylactic Acetaminophen May Blunt Immune Response to Vaccines

Prophylactic Acetaminophen May Blunt Immune Response to Vaccines

Prophylactic Acetaminophen Could Lower Response to Childhood Immunizations

Because of concern about febrile seizures or other potential complications, some practitioners prescribe prophylactic antipyretics after routine

Paracetamol for stroke: easy in practice, but not in trials

Hyperthermia exacerbates ischaemic neuronal injury and is associated with worse outcomes after stroke, including higher mortality, larger infarcts, and worse functional status. 1 Reith J Jorgensen HS Pedersen PM et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996; 347: 422-425 Summary Full Text PDF PubMed Scopus (782) Google Scholar , 2 Azzimondi G Bassein L Nonino F et al. Fever in acute stroke worsens prognosis: a prospective study. Stroke. 1995; 26: 2040-2043 Crossref PubMed Scopus (407) Google Scholar , 3 Hajat C Hajat S Sharma P Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke. 2000; 31: 410-414 Crossref PubMed Scopus (376) Google Scholar , 4 Wang Y Lim LL Levi C Heller RF Fisher J Influence of admission body temperature on stroke mortality. Stroke. 2000; 31: 404-409 Crossref PubMed Scopus (191) Google Scholar Inducing hypothermia, or at least avoiding hyperthermia, would seem to be promising neuroprotective strategies in acute stroke, although achieving either easily, quickly, and effectively for the millions of people worldwide who have stroke each year has proven challenging. Technological advances have yielded indwelling central venous cooling catheters, surface-cooling pads, even intranasal cooling devices, all of which are being tested in stroke trials, but for much of the world, something simpler and cheaper is needed. Widely available, paracetamol is a possible part of the solution. Several small clinical trials have tested paracetamol as a treatment for acute stroke, finding a consistent reduction in temperature of only about 0·25°C and a possible small reduction in occurrence of fever but no effect on clinical outcome. 5 Dippel DW van Breda EJ van Gemert HM et al. Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke. 2001; 32: 1607-1612 Crossref PubMed Scopus (147) Google Scholar , 6 Kasner SE Wein T Piriyawat P et al. Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. Stroke. 2002; 33: 130-134 Crossref PubMed Scopus (159) Google Scholar , 7 Koennecke HC Leistner S Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study. Neurology. 2001; 57: 2301-2303 Crossref PubMed Scopus (58) Google Scholar , 8 Kalafut MA Llanes J Kidwell C Starkman S Saver JL Can prophylactic acetaminophen prevent hyperthermia in acute stroke? Results of the normothermia and stroke outcomes (NOTHOT) pilot clinical trial. Stroke. 2001; 32 (abstr).: 381 Google Scholar , 9 Dippel DW van Breda EJ van der Worp HB et al. Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]. BMC Cardiovasc Disord. 2003; 3: 2 Crossref PubMed Scopus (91) Google Scholar The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trialThese results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37–39°C, but this post-hoc finding needs further study. Full-Text PDF

Acetaminophen and Ibuprofen for Prevention of Adverse Reactions Associated with Childhood Immunization

To evaluate the literature examining prophylactic use of acetaminophen and ibuprofen for prevention of adverse reactions associated with childhood immunization. Articles were identified via MEDLINE/PubMed/EMBASE (1966-March 2007) using the following key terms: vaccination, immunization, diphtheria-tetanus toxoids-whole pertussis (DTwP), diphtheria tetanus-toxoid, whole pertussis, diphtheria-tetanus toxoids-acellular pertussis (DTaP), acellular pertussis, Haemophilus influenzae type B, inactivated poliovirus, pneumococcal 7-valent conjugate, measles, mumps, rubella, meningococcal C-conjugate, varicella zoster, hepatitis B, influenza, pneumococcal polysaccharide, adverse reactions, analgesics, antipyretics, acetaminophen, ibuprofen, infant, and child. No limitations were placed on article selection. Five articles examining the effects of prophylactic acetaminophen or ibuprofen for adverse effects associated with either DTaP or DTwP vaccine were retrieved. In one randomized controlled trial of children aged 4-6 years given DTaP, no effect of prophylactic acetaminophen 15 mg/kg/dose, up to 450 mg, or ibuprofen 10 mg/kg/dose, up to 300 mg, was found on the incidence of fever, redness, pain, swelling, or itching. In 3 randomized studies of DTwP, either acetaminophen 10-15 mg/kg/dose or ibuprofen 20 mg/kg/24 hours, given in 3 equal doses before or at the time of immunization and every 4-8 hours thereafter for 12 or more hours, reduced fever, pain, fussiness, and local redness in infants 2-7 months of age compared with placebo. Results were not duplicated in older infants/children. No studies investigated use of prophylactic acetaminophen or ibuprofen for any other vaccine. Use of prophylactic acetaminophen and ibuprofen may reduce the incidence of adverse reactions in young infants receiving DTwP vaccine; however, DTwP has been replaced with DTaP, and no benefits have been demonstrated for this vaccine when evaluated in children aged 4-6 years, or with any other vaccine currently in use. Thus, neither drug can be recommended prophylactically to prevent vaccine-associated adverse reactions. Individuals at high risk for seizures may, however, warrant special consideration.

Can Prophylactic Acetaminophen Prevent Hyperthermia in Acute Stroke?: Results of the Normothermia and Stroke Outcome (NOTHOT) Pilot Clinical Trial

P232 Objective: To explore the safety and efficacy of round-the-clock acetaminophen administration to prevent hyperthermia in acute ischemic stroke patients. Background: Fever is a frequent occurrence among stroke patients and large cohort studies have identified early fever as an independent risk factor for poor functional outcome. Conventional management is to use antipyretics only in response to the appearance of fever. A pre-emptive strategy of prophylactic antipyretic therapy has not been previously studied. Methods: Sixteen consecutive patients presenting within 24 hrs of ischemic infarction were given acetaminophen 650mg q 4 hrs for 72 hrs or until discharge. Oral temperatures were recorded q 4 hrs. Cooling blankets were ordered for T &gt;37.6 0 C. These results were contrasted with a historical control cohort of 16 consecutive patients who were admitted within 24 hrs of stroke onset treated with conventional reactive antipyretic therapy. Results: In the acetaminophen group, mean age was 71.4 and 62.5% were male. Mean admission NIHSS score was 8.9. Mean time from stroke onset to first dose of acetaminophen was 12.9 hrs. Mean temperature at presentation was 36.6 0 C for the acetaminophen group vs. 36.4 0 C for controls (p=NS). 44% of the acetaminophen group developed elevated body temperature vs. 40% of controls (p=NS). Mean temperature during the first 24 hrs of treatment with acetaminophen was 36.8 0 C vs. 36.8 0 C for controls. Corresponding numbers for the second and third 24-hour periods were 36.9 0 C for the acetaminophen group vs. 37.1 0 C for controls (p=0.02) and 36.9 0 C for the acetaminophen group vs. 36.9 0 C for controls. Across the 72 hr treatment period, mean temperature was 36.9 0 C for the acetaminophen group vs. 37.0 0 C for controls (p=0.05). Conclusion: This pilot trial demonstrates acetaminophen administered round the clock significantly lowers average body temperature in the first 72 hrs after ischemic stroke. A randomized controlled clinical trial is needed to determine whether acetaminophen mediated body temperature lowering results in smaller infarct volume and improved clinical outcomes.

Can Prophylactic Acetaminophen Prevent Hyperthermia in Acute Stroke?: Results of the Normothermia and Stroke Outcome (NOTHOT) Pilot Clinical Trial

P232 Objective: To explore the safety and efficacy of round-the-clock acetaminophen administration to prevent hyperthermia in acute ischemic stroke patients. Background: Fever is a frequent occurrence among stroke patients and large cohort studies have identified early fever as an independent risk factor for poor functional outcome. Conventional management is to use antipyretics only in response to the appearance of fever. A pre-emptive strategy of prophylactic antipyretic therapy has not been previously studied. Methods: Sixteen consecutive patients presenting within 24 hrs of ischemic infarction were given acetaminophen 650mg q 4 hrs for 72 hrs or until discharge. Oral temperatures were recorded q 4 hrs. Cooling blankets were ordered for T >37.6 0 C. These results were contrasted with a historical control cohort of 16 consecutive patients who were admitted within 24 hrs of stroke onset treated with conventional reactive antipyretic therapy. Results: In the acetaminophen group, mean age was 71.4 and 62.5% were male. Mean admission NIHSS score was 8.9. Mean time from stroke onset to first dose of acetaminophen was 12.9 hrs. Mean temperature at presentation was 36.6 0 C for the acetaminophen group vs. 36.4 0 C for controls (p=NS). 44% of the acetaminophen group developed elevated body temperature vs. 40% of controls (p=NS). Mean temperature during the first 24 hrs of treatment with acetaminophen was 36.8 0 C vs. 36.8 0 C for controls. Corresponding numbers for the second and third 24-hour periods were 36.9 0 C for the acetaminophen group vs. 37.1 0 C for controls (p=0.02) and 36.9 0 C for the acetaminophen group vs. 36.9 0 C for controls. Across the 72 hr treatment period, mean temperature was 36.9 0 C for the acetaminophen group vs. 37.0 0 C for controls (p=0.05). Conclusion: This pilot trial demonstrates acetaminophen administered round the clock significantly lowers average body temperature in the first 72 hrs after ischemic stroke. A randomized controlled clinical trial is needed to determine whether acetaminophen mediated body temperature lowering results in smaller infarct volume and improved clinical outcomes.

Immunogenicity and adverse reactions of influenza vaccination in elderly patients given acetaminophen or placebo

The objective was to examine the antibody responses to influenza immunization in an elderly population and the effect of prophylactic acetaminophen on adverse responses due to inactivaed whole virus vaccine containing influenza A (H3N2 and H1N1) and B antigens. During the autumn of 1990, 100 patients 65 years or older were immunized and randomly allocated to receive placebo or 1,950 mg (2 × 975 mg) of acetaminophen. They recorded any local and systemic side effects over a 3-day period. Serology was performed on pre- and post (4–6 weeks) -vaccination sera. Age and gender distribution in the study were: 47% who were 75 years or older, and 61% of the patients were female. Most of the patients (97%) had pre-existing antibodies to Influenza A or B. Average peak preimmunization antibody titers were 40 to B Yamagata and A Taiwan (H1N1) and 80 for A Shanghai (H3N2). Half of each treatment group had a 4-fold or greater rise in antibody titer in response to the vaccine. Only 30% of patients immunized the previous year but 80% of those never vaccinated previously demonstrated a 4-fold or greater serological response to the vaccine. However, measurement of protection rates (HI⩾40) before and after vaccination indicated 81.1–100% protection for the 3 viruses not influenced by treatment, gender or a history of previous vaccination. Both treatment groups had equally small numbers of patients who recorded systemic symptoms of drowsiness, myalgia, fever and chills and about 50% had arm soreness. Although about 80% of previously unimmunized adults mounted a 4-fold antibody rise to influenza vaccine antigens whereas booster effects were seen in only 30% of those immunized the previous year, protection rates were high (81–100%) after immunization and were not affected by acetaminophen treatment. Adverse effects (15% systemic and 50% local) were not ameliorated by 1950 mg of acetaminophen in these elderly patients.

Are We Sweeping DTP Contraindications Under the Rug?-Reply

In Reply .—In expressing concern about the widespread use of prophylactic acetaminophen in children receiving DPT vaccine, Dr Brauer speculates on the possibility that acetaminophen might mask a harbinger of a subsequent severe reaction. However, as he correctly implies, no relationship between certain reactions to pertussis vaccine, such as fever and temporally associated neurological events (other than febrile convulsions), has been established. In fact, the risk of giving DPT vaccine to a child who has had a prior severe febrile reaction, ie, temperature greater than 40.5°C, has not been evaluated, and in all probability never will be. The reason DPT vaccine is contraindicated in such circumstances is based on the unproved but reasonable presumption that children with severe adverse reactions following immunization are more likely to have similar reactions on repeated vaccination. While acetaminophen may lessen the likelihood of a severe febrile reaction and prevent some convulsions, postvaccination seizures have not been