PRN Group Research Articles

Differences in the Prevalence and Severity of Side Effects Based on Type of Analgesic Prescription in Patients with Chronic Cancer Pain

An understanding of the relationship between the type of analgesic prescription and the prevalence and severity of side effects is crucial in making appropriate treatment decisions. The purposes of this study were to determine if there were differences in the prevalence of side effects among four different types of analgesic prescriptions (i.e., no opioid, only an as needed (PRN) opioid, only an around-the-clock (ATC) opioid, or an ATC + PRN opioid); to determine if there were differences in the severity of side effects among the four prescription groups; and to determine the relationships between the total dose of opioid analgesic medication prescribed and taken and the severity of side effects. As part of a larger study, 174 cancer patients with bone metastasis reported their analgesic use and the prevalence and severity of 11 side effects. Significant differences ( P < 0.05) were found in prevalence rates for seven of the side effects among the four prescription groups. The highest prevalence rates were found in the only ATC and ATC + PRN groups. Significant differences were found in the severity scores for five of the side effects, with the highest severity scores reported by patients in the only ATC and ATC + PRN groups. Significant positive correlations were found between the severity of six of the side effects and the total dose of opioid prescribed and taken. Risk factors for analgesic-induced side effects are ATC and ATC + PRN prescription types and higher doses of opioid analgesics.

Time-Contingent Dosing of an Opioid Analgesic After Tonsillectomy Does Not Increase Moderate-to-Severe Side Effects in Children

As part of a randomized clinical trial that compared three different analgesic dosing regimens ( Sutters et al., 2004), the purpose of this study, in children who underwent tonsillectomy, was to determine whether around-the-clock (ATC) dosing of acetaminophen with codeine, compared with as-needed (PRN) dosing, increased the frequency of moderate-to-severe opioid-related side effects (i.e., daytime sedation, lightheadedness, nightmares, nausea, vomiting, and constipation) in the first 3 days after surgery. Because no differences were found in pain intensity scores and in the amount of analgesic administered between the two ATC groups (i.e., with and without coaching), for these analyses, the two groups were combined ( n = 52) and compared with the PRN group ( n = 28). Each side effect was recoded into a dichotomous response (i.e., 0 = did not have symptoms or had slight symptoms; 1 = symptoms that were moderate, severe, or very severe) to provide an adequate sample size in each cell for the statistical analyses. No differences were found in the frequency of moderate-to-severe side effects between the ATC and PRN groups at any of the postoperative assessments. The number of children who reported moderate-to-severe daytime sedation decreased over time in both the PRN ( p = .02) and ATC groups ( p = .01). Children in the ATC groups reported a statistically significant decrease over time in vomiting ( p = .001) and feeling lightheaded or dizzy ( p = .003), and a significant increase in constipation ( p = .018). Except for daytime sedation, changes, over time, in the frequency of moderate-to-severe side effects were not observed in the PRN group.

Postoperative behavioral changes in children after tonsillectomy

The purpose of this randomized clinical trial, with children undergoing tonsillectomy, was to compare changes in the child’s postoperative behavior with “as needed” or around-the-clock analgesic dosing. Children were randomized to receive acetaminophen with codeine (12mg/5ml) for 3 days after surgery every 4 hours “as needed” (PRN Group: N=28) or every 4 hours around-the-clock (ATC Group: N=52). Parents were asked to compare each behavior listed in the home log with the child’s normal behavior before surgery, and record observed behavioral changes once a day, beginning on the day of surgery and for the first three days after surgery.

A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy

The purpose of this study was to determine whether around-the-clock (i.e. ATC) dosing of acetaminophen with codeine, with or without nurse coaching, compared to standard care with as needed (i.e. PRN) dosing: reduced children's reports of pain intensity with and without swallowing; increased pain relief, and increased analgesic consumption. Eighty children, 6–15 years, undergoing tonsillectomy were randomized to one of three treatment groups to receive acetaminophen with codeine (120 mg/12 mg/5 ml) for 3 days after surgery: PRN group ( N=28)—every 4 h PRN, with standard postoperative instructions, without nurse coaching; ATC group ( N=26)—every 4 h ATC, with standard postoperative instructions, without nurse coaching; and ATC+coaching group ( N=26)—every 4 h ATC, with standard postoperative instructions and nurse coaching. In all three groups, significant decreases were found over time in pain intensity scores at rest ( P<0.0001) and with swallowing ( P<0.0001). However, mean pain scores at rest and with swallowing were >3/10 until the fourth evening after tonsillectomy. Children in both ATC dosing groups received significantly greater amounts of acetaminophen and codeine than children in the PRN group ( P<0.003). No significant differences were found in the amount of analgesic administered between the ATC dosing groups with and without nurse coaching. No significant differences were found in the amount of nausea and vomiting among the three groups. Scheduled dosing of acetaminophen with codeine did not provide adequate pain relief for children following tonsillectomy. Nurse coaching does not increase parent's adherence with an ATC dosing schedule.

Increased epithelial cell proliferation in very premature baboons with chronic lung disease.

Coordinated proliferation of lung cells is required for normal lung growth and differentiation. Chronic injury to developing lung may disrupt normal patterns of cell proliferation. To examine patterns of cell proliferation in injured developing lungs, we investigated premature baboons delivered at 125 days gestation (approximately 67% of term) and treated with oxygen and ventilation for 6, 14, or 21 days (PRN). Each PRN treatment group contained 3 or 4 animals. During normal in utero lung development, the proportion of proliferating lung cells declined as measured by the cell-cycle marker Ki67. In the PRN group, the proportion of proliferating lung cells was 2.5-8.5-fold greater than in corresponding gestational controls. By 14 days of treatment, the proportion of cells that expressed pro-surfactant protein B (proSP-B) was ~2.5-fold greater than in gestational controls. In the PRN group, 41% of proliferating cells expressed proSP-B compared with 5.8% in the gestational controls. By 21 days of treatment, proliferation of proSP-B-expressing epithelial cells declined substantially, but the proportion of proliferating non-proSP-B-expressing cells increased approximately sevenfold. These data show that the development of chronic lung disease is associated with major alterations in normal patterns of lung-cell proliferation.

Oncology outpatients with pain from bone metastasis require more than around-the-clock dosing of analgesics to achieve adequate pain control

Around-the-clock (ATC) dosing of opioid analgesics is the established approach for the management of chronic cancer pain. The purposes of this study were to determine whether there were differences in pain intensity scores and pain duration between oncology outpatients who were taking opioid analgesics on an around-the-clock (ATC) compared with an as needed (PRN) basis and to determine differences in opioid prescription and consumption between the 2 groups during a period of 5 weeks. Oncology patients (n = 137) with pain from bone metastasis were recruited from 7 outpatient settings. Patients completed a demographic questionnaire and on a daily basis recorded pain intensity scores and medication intake in a diary. No significant differences in average, least, or worst pain intensity scores or number of hours per day in pain were found between the 2 groups. However, the average total opioid dose, prescribed and taken, was significantly greater for the ATC group than for the PRN group. These findings suggest the need for further investigations in the following areas: the appropriate treatments for pain related to bone metastasis, the use of various pain measures to evaluate the effectiveness of analgesic medications, and the need to evaluate how analgesics are prescribed and titrated for patients with cancer-related pain. © 2002 by the American Pain Society

Differences in Morphine Consumption Administered by PCA and Traditional IV Methods in a Pediatric Population

The undertreatment of pediatric postoperative pain has been a persistent problem. This study compared postoperative morphine use between two groups of pediatric patients, those receiving intravenous (IV) morphine either as needed (PRN) or via patient-controlled analgesia (PCA). The study's objectives were to measure the mean amounts of morphine used by each group and lo determine if these amounts were significantly different. Data collection involved a retrospective review of 113 charts of patients who had undergone appendectomy surgeries. Results showed that patients in the IV PRN group used significantly less morphine postoperatively compared to the IV PCA group, controlling for demographic and clinical variables. Potential implications of these findings and recommendations for future research are offered.

Endogenous Pulmonary Nitric Oxide In The Preterm Baboon: Relationship To Gestational Age and Developing Chronic Lung Disease. † 1511

Increased levels of nitric oxide (NO) have been measured in exhaled gas in a variety of pulmonary pathologies with a prominent inflammatory component. Inflammation with both the appearance of inflammatory cells and elevation of a variety of inflammatory mediators appears to be a consistent component in the pathology of hyaline membrane disease (HMD) and early neonatal chronic lung disease (CLD). We report pulmonary NO production in the baboon model of HMD and CLD. Ten premature baboons, Papio sp., at 140 days (77%) gestation were delivered by hysterotomy and placed on IMV at an FiO2=1.0 (5 animals-induced HMD/CLD), or at an FiO2 adjusted “prn” (5 animals- controls) to maintain normal arterial oxygen levels. Four additional baboons were delivered at 125 days (70%) gestation and were managed on IMV with FiO2 adjusted “prn.” Gas was sampled and measurements were paired from both the proximal limb of the ventilator(<2 ppb), and endotracheally via a double lumen endotracheal tube at hour of life 1,2,4, and every 4 hours until necropsy at 144 or 240 hours. The sampled gas was analyzed by chemiluminescence after verification of baseline with “zero” gas, and calibration to known NO gas standards. The resulting digital signal was recorded and subsequently processed to yield peak NO levels in parts per billion (ppb) for each respiratory cycle. Comparisons were analyzed with one way ANOVA with correction for repeated measures and Student-Newman-Keuls method. Overall mean peak endotracheal NO levels measured at the distal ETT in the two gestational ages were: 140 day gestation prn animals 5.2 ppb (95% confidence interval 0.8 ppb), 125 day gestation prn animals 2.4 ppb (95% confidence interval 0.3 ppb). Comparison at each sampling time revealed a significantly lower (p=0.004) mean peak endotracheal NO levels over the first 28 hours of life in the 70% gestation animals. No statistically significant differences were found between the 140 day gestation prn group and the FiO2=1.0 group. No correlation was found when comparing mean peak endotracheal NO levels with a/AO2 ratio or oxygenation index. Endogenous pulmonary production of NO measured endotracheally in the intubated premature baboon appears to be significantly lower at earlier gestational ages. Despite evidence suggesting the importance of inflammation in the evolution of CLD, exhaled NO levels do not appear to increase in this primate model of neonatal CLD.

Sodium cromoglycate eye drops: Regular versus “as needed” use in the treatment of seasonal allergic conjunctivitis

Objective: The objective of this study was to compare the efficacy and side effects of sodium cromoglycate eye drops (Opticrom 2%) used regularly versus as needed in the treatment of seasonal (ragweed) allergic conjunctivitis. Methods: A randomized, unblinded, parallel group comparison was performed during the 6 weeks of the ragweed pollen season. Sixty-two adults with ragweed pollen–induced conjunctivitis were recruited for the study from previous ragweed studies and notices in the local media. Two drops of sodium cromoglycate were placed in each eye either four times daily (regular treatment group) or when needed, up to four times daily (prn group), from 1 week before and throughout the ragweed pollen season. Uncontrolled eye symptoms were treated with terfenadine 60 mg as needed, up to 120 mg daily. Subjects kept daily diaries for symptoms and medication requirements throughout the 6 weeks of treatment. The Rhinoconjunctivitis Quality of Life Questionnaire was administered and adverse experiences were reported after 1, 3, and 6 weeks of treatment. Results: Diary eye symptoms were similar in the two treatment groups, but quality of life was better in the regular treatment group. There was a trend for the prn group to require more terfenadine for uncontrolled eye symptoms. Conclusions: There may be some additional therapeutic benefit from using sodium cromoglycate eye drops regularly throughout the ragweed pollen season. (J ALLERGY CLIN IMMUNOL 1994;94:36-43.)

Aqueous beclomethasone dipropionate in the treatment of ragweed pollen-induced rhinitis: Further exploration of “as needed” use

Background: The objective of this study was to compare regular and “as required” (prn) use of aqueous beclomethasone dipropionate nasal spray (Beconase AQ nasal spray) in the treatment of ragweed pollen-induced rhinitis and to examine possible predictors of unsatisfactory symptom control in the group of patients who used it on a prn basis. Methods: Sixty adults with ragweed pollen-induced rhinitis, who had participated in previous hay fever studies or who responded to media notices, were enrolled in the study. The study design was a randomized, unblinded, parallel group comparison between regular use (400 μg daily) and prn use of Beconase AQ spray during the 6 weeks of the ragweed pollen season. Patients recorded daily symptoms and medication use in diaries. The Rhinoconjunctivitis Quality of Life Questionnaire was administered, and patient satisfaction with symptom control was assessed at clinic visits. Results: Symptoms and quality of life tended to be better in the regular group, but differences were not statistically significant. Twenty-seven percent of patients in the prn group reported unsatisfactory control of symptoms; they experienced significantly worse symptoms and quality of life than the remainder of the prn group and used significantly more Beconase. No obvious predictors of unsatisfactory control were identified. Patients who achieved satisfactory control in the prn group had symptom and quality of life scores that were very similar to those of the regular group. Conclusions: Most patients can use Beconase AQ as needed successfully for the treatment of hay fever, but there may be an apparently unpredictable minority who do not achieve satisfactory symptom control or quality of life with this approach and who require regular treatment.

Pathophysiologic, morphometric, and biochemical studies of the premature baboon with bronchopulmonary dysplasia.

Pathophysiologic, morphometric, and biochemical (surfactant and coagulation-fibrinolytic parameters) features were studied in premature baboons with and without bronchopulmonary dysplasia (BPD). A total of 22 baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group 1 (PRN) animals were ventilated with high-frequency oscillation for 48 to 72 h and then changed to positive-pressure ventilation (PPV) while maintained on clinically appropriate oxygen for the 21-day experimental period. Group 2 (BPD) animals were ventilated with PPV and 1.0 FlO2 for 7 days followed by 0.8 FlO2 for 14 days. Group 3 (control) animals were delivered and immediately killed at 140 days gestation. Group 1 animals showed no significant airway or saccular lesions, and alveolarization of the saccules was present. Group 2 animals showed metaplastic or hyperplastic epithelial lesions in airways and an alternating pattern of atelectatic but more normal appearing saccules and alveoli interposed between foci of thickened overexpanded saccular walls with no alveolarization. Differences within and between the three study groups were analyzed morphometrically. When numerical densities were examined by comparing control, PRN, BPD-atelectatic areas, and BPD-overexpanded areas. Type II cells were significantly increased in the BPD-overexpanded sites above those of control and PRN values. The interstitial cells were significantly more numerous in the BPD-atelectatic blocks compared with control and BPD-overexpanded blocks. Endothelial cell numerical densities were significantly decreased in the overexpanded sites of the BPD animals compared with the control, PRN, and BPD-atelectatic values. Volume density data showed that the interstitial compartment of the BPD group was significantly larger than those of the control and PRN groups. This was seen as significant increases in the cellular, noncellular, and connective tissue fiber components. Vascular endothelium or lumen volume densities were not different between the BPD and PRN animals, but did differ from those of the 140-day gestation controls. Comparable levels of lavage plasminogen-dependent fibrinolytic activity, were detectable at the 21-day study interval. The phospholipid composition of pulmonary surfactant, including disaturated PC and total PG, was similar between BPD and PRN groups at 21 days. The pathologic, morphometric, and biochemical patterns in this study probably represent those seen in human neonates with mild to moderate clinical BPD who survive. At this time, it is not known if the destructive endothelial lesion and the lack of alveolarization in the overexpanded and fibrotic lesions will resolve over time in long-term BPD survivors.

Reduction of post-operative morbidity following patient-controlled morphine

The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery.