ReviewerCommentResponseApplies to section of report
Karl LorenzOverall, the review provides a helpful summary of clinical questions relevant to expanding pain services, developing standards, and prioritizing a research agenda to improve inpatient pain management in medical settings for veterans. They review found little direct evidence to guide acute pain management in medical inpatients, excluding patients with cancer, those in late life, and the surgical settings.NotedGeneral comment
Roger ChouI think the report does a good job of summarizing the (lack of) evidence for most of the pain management practices in the inpatient setting.NotedGeneral comment
Bob KernsI am reading with considerable interest this review. One question is puzzling me: I had thought that the review would also include management of pain in surgical settings (note the title of the abstract). Is your intention to provide a separate review with this focus, or did you decide to limit your attention to non surgical, acute medical settings? Or did we simply miscomunicate our intentions?Regarding the scope, note that before we began the review the ESP committee agreed to a statement that says “Patients with post operative pain, sickle cell disease, and cancer pain, and patients who have been hospitalized 10 days or longer, are excluded.”Scope and key questions
Roger Chou1) Exclusion of sickle cell patients: I don't remember the justification for excluding sickle cell patients, but it might seem funny to readers/users of the report because sickle cell is probably the population with the most data on pain management in the inpatient setting. I think the reasoning for exclusion should at least be described. Also, it seems a bit inconsistent that evidence on outpatients and cancer pain patients and post op are mentioned in relevant spots but sickle cell evidence is generally not described and is arguably more (or just as) relevant.See above.Scope and key questions
Karl Lorenz1. The evidence tables cite about 25 retained studies. 390 studies were reviewed in detail. An accounting of the reasons for exclusion is needed, as well as a summary description of retained studies – overlap and relevance of titles for each question, and a description of the study designs used to answer each question.This infomation is available upon request.Results
Karl Lorenz2. A very brief quantitative summary of the studies included at the beginning of each section would be helpful.Agree.Results
Karl Lorenz3. It is somewhat confusing to have the systematic reviews cited in the text for evidence, but for them to be missing in the tables (which may be used by some readers as the primary source of information). I suggest you include a ‘systematic review table’ in which you highlight the evidence related to each review (e.g., systematic reviews cited in text for pca as refs 5766 and so forth) – relevant to each question and note that the current tables are ‘other studies’ not covered in the reviews (if that’s the case).AgreeResults; evidence tables
Jack RosenbergWhat is obvious is that the search strategy for this may be flawed. Namely, specific disease entities that make up acute non surgical pain were not searched. I also did not see the years of publications that were covered. Much of the literature may be old. Just looking at kidney stone pain for 30 minutes, I pulled these four articles that describe treatment of pain for this entity that are not covered in this review. I did not have the time to go and pull the supporting references.

So for a brief synopsis of my opinion, the search for articles should be repeated looking at the questions in reference to particular entities that make up acute pain. for example acute fractures of hip, pelvis, spine)), abdominal, including pancreatic and others. I am also not sure that excluding exacerbations of chronic pain (also called acute on chronic pain) serves us well. There is not much literature on this subject, but these suggestions should help increase the information for analysis.
Our initial searches used broader terms than the specific disease entities; in a supplemental search, using the disease names did not identify additional relevant literature. We alsp conducted a series of supplemental searches relaxing other criteria used in the original searches. These identified 76 potentially relevant abstracts. One of these was a randomized trial of morphine for acute abdominal pain in the emergency room which supported the findings of a systematic review (by Ranji et al) of 12 trials but was too recent to be included in that review. The others concerned clinical settings and conditions that were excluded from our review.Methods; search strategy
Roger Chou2) The quality of included studies is summarized in the appendix tables and in the summary table but is not always clear when reading the text. I don't think you need to spend a lot of time describing quality of non RCTs but for RCTS and when describing results of SR's it is probably important to make some mention about quality of the RCTs or studies included in the SR's.AgreeResults: systematic reviews
Roger Chou3) Regarding KQ #2, some guidelines recommend against use of IM opioid b/c they are equally well absorbed SQ (based on PK data) and this probably should be mentioned at least as background info. Also, there are some old RCTs in cancer pain setttings showing no difference between rectal and oral morphine (Beaver WT 1967 [2 studies]), or IM vs. oral opioids (Babul N 1998 and De Conno F 1995) if you want to describe results from other populations.This pertains to question 2d. In the section on renal colic we said: “Most evidence about treating renal colic is old and addresses whether to use IM or IV analgesics. The main findings, discussed in more detail below, are (1) NSAIDs provide effective analgesia for acute renal colic, and act more quickly through the IV route than by IM or PR 2) Opioids provide analgesia that is equivalent to NSAIDs but result in a higher incidence of vomiting and other adverse events, particularly pethidine 3) Hydromorphone provided superior pain relief and led to fewer hospital admissions compared with meperidine in one study.” We revised this to make the point suggested by the reviewer.Results: KQ#2
Roger Chou4) The section on PCA doesn't talk about use of basal infusion + prn versus prn only. My understanding is that some studies suggest that the basal infusion increases opioid use but doesn't improve pain, but I don't have any studies to cite for that. I do think it's a pretty common question on the inpatient setting though, with some people being taught to use basal infusions depending on how much opioid the patient required the previous day etc. Might be worth mentioning as an issue and the evidence (or lack thereof).This is an important issue clinically, but it is beyond the level of resolution of the literature about nonsurgical pain control. That is, we didn't find any literature about it in the target population.Results: PCA
Karl LorenzReviewer provided detailed advice for restructuring the future research section (see attached review)Agree with reorganizing this section using the reviewer's proposed outline.Future Research Section

From: APPENDIX D, Reviewer Comments and Responses - VA ESP Acute Pain Management in Inpatients

Cover of Assessment and Management of Acute Pain in Adult Medical Inpatients
Assessment and Management of Acute Pain in Adult Medical Inpatients: A Systematic Review [Internet].
Helfand M, Freeman M.
Washington (DC): Department of Veterans Affairs (US); 2008 Apr.

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