These patients often receive preoperative opioid treatment, making postoperative pain treatment difficult to manage.46, Adequate postoperative pain relief improves patient satisfaction and patients' perception of the quality of their hospital stay, and it facilitates early mobilization and optimal rehabilitation.9,35,36 However, there is a lack of consensus regarding the gold standard of the postoperative pain treatment strategy in patients undergoing 1- or 2-level lumbar spinal fusion procedures.46,47. From those, 10 trials demonstrated a significant effect on opioid consumption/supplemental analgesics11,15,18,19,25,29,33,38,39,73 and 12 studies on pain scores.11,13,15,18,19,25,29,33,38,40,57,73 Four trials demonstrated a significant reduction in opioid-related adverse events.13,39,65,69. 9 Radiographically, osseous fusion is defined by the development of bridging trabecular bone. Concerning secondary outcomes, significant reductions in pain scores were detected after 6 hours at rest (NSAID [P < 0.0001] and intrathecal morphine [P < 0.0001]), 6 hours during mobilization (intrathecal morphine [P = 0.003]), 24 hours at rest (epidural [P < 0.00001] and ketamine [P < 0.00001]), and 24 hours during mobilization (intrathecal morphine [P = 0.03]). Hence, 44 trials remained for the final data extraction randomizing 2983 participants13,57,1115,18,19,21,22,24,25,29,32,33,3841,43,44,52,53,5557,5962,6466,68,69,7174 (Fig. Supplemental digital content associated with this article can be found online at https://links.lww.com/PR9/A157. 10 minutes before skin closure, 1: (n = 32) ketamine i.v. [58]. 2). Your privacy choices/Manage cookies we use in the preference centre. The quality of evidence (GRADE) was moderate (Table 2). c Volume of the psoas muscles. PDF Cervical Anterior Fusion Post-operative Rehabilitation Protocol Go to: 2. France JC, Jorgenson SS, Lowe TG, Dwyer AP. infusion of 1 g/kg/min after bolus 0.5 mg/kg, before skin incision + continued 48 hours postoperatively, 1: (n = 40) celecoxib 200 mg, pregabalin 75 mg, acetaminophen 500 mg, extended-release oxycodone 10 mg 1 hour preop + twice daily, 1: (n = 12) magnesium 50 mg/kg i.v. Tabaraee E, Ahn J, Bohl DD, Phillips FM, Singh K. Quantification of multifidus atrophy and fatty infiltration following a minimally invasive microdiscectomy. Dehkordy ME, Tavanaei R, Younesi E, Khorasanizade S, Farsani HA, Oraee-Yazdani S. Effects of perioperative magnesium sulfate infusion on intraoperative blood loss and postoperative analgesia in patients undergoing posterior lumbar. Hernandez-Palazon, Tortosa JA, Martinez-Lage JF, Prez-Flores D. Intravenous administration of propacetamol reduces morphine consumption after. 1: (n = 30) bupivacaine 0.25%, 20 mL erector spinae block, 1: (n = 13) ropivacaine 0.1% 12 mL/hr during surgery; epidural postoperatively, Acetaminophen (1 g x 4 daily), ketoprofen (100 mg x 2 daily) nefopam (20 mg x 4 daily), 1: (n = 19) ropivacaine 10 mL bolus + 8 mL/h for 48 hours; end of surgery; wound infiltration, 1: (n = 15) ketamine i.v. Unfortunately, they do not investigate opioid consumption. In this systematic review of pain management after 1- or 2-level spinal fusion surgery, we identified 5 significant subgroups dealing with the following analgesic treatment: NSAIDS, epidural, ketamine, wound infiltration, and i.t. Ultrasound-guided erector spinae plane block for acute, [21]. Ketamine as an adjunct to postoperative. Loading dose + i.v. 1993;18(5):57581. Sihvonen T, Herno A, Paljarvi L, Airaksinen O, Partanen J, Tapaninaho A. The quality of evidence (GRADE) was low (Table 2). Cite this article. Reviews of pain treatment in mixed or complex spine surgery indicate that use of paracetamol, NSAIDs, i.v. Keyword Highlighting Murakami N, Obata K, Abe Y, Oto Y, Kido Y, Itabashi H, et al. As shown in Table2, although there was no statistically significant difference (p>0.05), the height of the vertebrae (the distance between the L3 lower endplate and the S1 upper endplate) increased by 0.50.8mm in both the MRI and CT groups. We performed this systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.49 Before performing the literature search, we registered the protocol at PROSPERO, the international prospective register of systematic reviews on July 26, 2020, registration number: CRD42020192899. Radiologic parameters were measured using MRI or CT images which were taken before surgery and at 1year after surgery. The results showed a significant reduction in opioid consumption for treatment with NSAID (P < 0.0008) and epidural (P < 0.0006) (predefined minimal clinical relevance of 10 mg). The clinical and radiological data were collected in accordance with the regulations of the institutional review board at our hospital. Trial sequential analysis showed that the required information size was not reached, but the DARIS line was crossed (Appendix 3, available at https://links.lww.com/PR9/A157). After lumbosacral fusion, changes in the forces acting on the sacrum and pelvis may occur. Tabaraee et al. J Orthop Surg Res 2018;13:1518. Geisler A, Dahl JB, Karlsen AP, Persson E, Mathiesen O. Wen X, Huang Y, Chen Y, Fang S, Wu S. Clinical research on postoperative analgesia effect of using dezocine before suturing skin in patients with internal fixation of spine. We designed a broad search string, including MeSH and All fields terms, in collaboration with a professional search coordinator to avoid overlooking relevant trials (Appendix 1, available at https://links.lww.com/PR9/A157). Preemptive analgesia for postoperative, [3]. SKH: analysis and interpretation of data. Conversely, if a preoperative CT was performed at baseline then a CT was used in the follow up. The role of inflammatory mechanisms in neuropathies occurring after surgeries is poorly appreciated and not well characterized, and may provide a rationale for immunotherapy. Measuring inconsistency in meta-analyses Need for consistency. 4). However, when the paraspinal muscle volume was compared between the preoperative and postoperative images, there was a postoperative reduction of the MF, and this was consistently observed in the right and left side of both the MRI and the CT groups (Fig. CONCLUSION. Spinal fusion surgery is a major procedure with a lengthy recovery time. Furthermore, headache, shivering, paresthesia, hematoma, infection, hallucinations, visual disturbance, confusion, urine retention, and constipation were reported. Age- and level-dependence of fatty infiltration in lumbar paravertebral muscles of healthy volunteers. Postoperative pulmonary complications are among the main complications following posterior spinal instrumentation and fusion surgery in patients with CS. Comparisons of the muscle volumes between preoperative and 1year post-surgery images were made using paired t-test with Bonferroni post-hoc correction. Reisener M, Pumberger M, Shue J, Girardi FP, Hughes AP. Wolters Kluwer Health Article Eur Spine J. Paraspinal muscle changes after single-level posterior lumbar fusion: volumetric analyses and literature review, https://doi.org/10.1186/s12891-020-3104-0, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmusculoskeletaldisorders@biomedcentral.com. BMC Med Res Methodol 2017;17:3918. This review also has limitations. Su X, Wang DX. Spine. Remifentanil used as adjuvant in general anesthesia for, [73]. Effective dose of peri-operative oral pregabalin as an adjunct to multimodal analgesic regimen in lumbar, [40]. This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0 (CC BY-ND) which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. Most previous studies explored the effects of posterior lumbar fusion surgery on the paraspinal muscles by quantitative analysis of magnetic resonance imaging (MRI) or computed tomography (CT) images using specific software [4, 5, 9,10,11,12]. Br J Rheumatol. Even a minimally invasive spinal fusion can be painful and require a long recovery period. Spine. The heterogeneity was moderate, I2 = 79% (Fig. Google Scholar. We observed that the volume of the MF muscles was reduced after lumbar fusion surgery using a novel and simple formula. Syst Rev 2015;207:19. Yeom JH, Kim KH, Chon MS, Byun J, Cho SY. 1: (n = 21) propacetamol 2 g i.v. 3). Summary of background data: Degenerative cervical spinal disease is a common disorder, with . The height of this three-dimensional figure was defined as the distance between the L3 lower endplate and the upper endplate of S1 in the mid-sagittal image. Although we have not included this data, we also conducted regression analysis to determine the correlation between the gender and the changes in muscle volume; no significant correlation was observed. [46]. Adjacent segment degeneration is an undesirable condition seen after spinal fusion and is not uncommon . Posterior lumbar interbody fusion (PLIF) surgery is a widely accepted surgical technique for the treatment of LSS [ 1 ]. 1 hour before surgery, Ketorolac 30 mg i.v. 1). Spine. Of the 112 patients who underwent posterior lumbar interbody fusion (PLIF) surgery at the L4/5 level, 40 patients were included in the study (72 patients were excluded after applying the exclusion criteria). buprenorphine at 1 mL/h rate s.c. 1: (n = 16) buprenorphine 1.2 + 1 mg droperidol, total 48 mL, 1 mL/h for 48 hours after surgery; continuous s.c. infusion, Morphine 2 mg every 3 minutes Until VAS <4, 1: (n = 30) pregabalin 150 mg P.O., celecoxib 200 mg P.O., 2 hours before surgery, PCA fentanyl ketorolac 120 mg, ketorolac 30 mg i.v. 58 Patients undergoing this procedure are at a high risk of acute and persistent postoperative pain, development of postoperative hyperalgesia, and possibly opioid . The parameters measured in preoperative imaging were compared with those measured in the images obtained 1year after the surgery. Postoperative Care for Spinal Fusion Surgery | Spine-health The TSA showed that the required information size was not reached, but the DARIS line was crossed (Appendix 10, available at https://links.lww.com/PR9/A157). [17]. The mean age of the patients was 59.6years and 32 (80.0%) were female. 5 minutes before suturing the skin, PCA morphine morphine i.v. after skin incision; postop: paracetamol 1 g i.v. He had undergone a L5/S1 discectomy in 2001, which provided good symptomatic relief. Two authors performed bias assessment by using Cochrane's 7-step risk of bias tool.29, We performed meta-analyses and sensitivity analyses using Review Manager provided by Cochrane (RevMan version 5.4.1) whenever 3 or more trials reported the preplanned outcomes for continuous data regarding pain, opioid consumption, and postoperative nausea and vomiting (PONV). 2 In a multicentre study published in 2012, the authors suggested that the incidence of postoperative visual loss after spinal . Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Diclofenac 50 mg supp. The heterogeneity was moderate, I2 = 45% (Appendix 5, available at https://links.lww.com/PR9/A157). *Corresponding author. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. noted that both the psoas and extensor muscles reduced in size in CT studies after laminectomy and facetectomy, and that in addition to denervation, disuse or inactivity induced these atrophies [21]. Ghabach MMB, Mhanna NE, Abou Al Ezz MR, Mezher GN, Chammas MJ, Ghabach MMB. Asymmetric atrophy of multifidus muscle in patients with unilateral lumbosacral radiculopathy. Furthermore, it was impossible because of sparse data to report a reduced LOS regarding any analgesic treatment. [31]. Finally, 3 authors answered our questions. Histograms of the sum of right and left paraspinal muscles on MRI and CT. a Volume of the multifidus muscles. [54]. Wang Y, Guo X, Guo Z, Xu M. Preemptive analgesia with a single low dose of intrathecal morphine in multilevel posterior lumbar interbody fusion surgery: a double-blind, randomized, controlled trial. Privacy In the current study, atrophy of the MF was prominent; this was consistent with the findings of previous studies. Bum-Joon Kim. Therefore, we chose random-effects models to accommodate that. [16]. For pain during mobilization at 6 hours, 8 studies reported on VAS outcomes ranging from 17 to 71 mm, mean 46 mm for interventions and VAS 3279 mm, mean 57 mm for control groups. [26]. In the current study, the MF muscle showed a significantly decreased volume on both the MRI and CT images. You may be trying to access this site from a secured browser on the server. Anterior Cervical Discectomy and Fusion Complications - Spine-health Anaesthesia, surgery, and challenges in postoperative recovery. Imaging of postoperative spine fusion. Adolescent idiopathic scoliosis (IS) is a condition of unclear etiology that occurs in 1 to 3% of otherwise healthy children and adolescents and when severe can result in respiratory and cardiovascular deterioration. Urban MK, Ya Deau JT, Wukovits B, Lipnitsky JY. The summarized bias was high in 11, unclear in 26, and low in 7 trials (Fig. The quality of evidence (GRADE) was low (Table 2). First, Covidence removed 4239 duplicates, and after the abstract and full-text screening, we removed 20,080 trials. 1: (n = 20) dezocine 0.1 mg/kg i.v. Postoperative Spinal CT: What the Radiologist Needs to Know Does continuous wound infiltration enhance baseline intravenous multimodal analgesia after posterior. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painrpts.com). Moreover, studies not only need to focus on average pain in groups but also on the individual patient's pain.16. Waelkens P, Alsabbagh E, Sauter A, Joshi GP, Beloeil H. [68]. pointed out that the cause of postoperative atrophy was iatrogenic denervation of the paraspinal muscles during lumbar surgery [20]. The volume loss of the right ES in the CT group was negatively correlated with the age of the patients (p=0.016) (Table3); therefore, our data suggests that the younger patients experienced the greatest loss of muscle mass. Ketorolac 30 mg i.v. This systematic review aimed to provide answers about best-proven postoperative analgesic treatment for patients undergoing lumbar 1- or 2-level fusions for degenerative spine diseases. 5). The authors would like to thank Peter Udby for his contribution in screening trials for eligibility and Mathias Maagaard for providing advice regarding the statistics. h=vertical height (cm). In the regression analysis, the postoperative volume loss of both the right-sided and left-sided MF muscles showed a negative correlation with the age of the patients in the MRI groups (p=0.002 and p=0.015, respectively). Imaging Assessment of the Postoperative Spine: An Updated Pictorial Fujita N, Tobe M, Tsukamoto N, Saito S, Obata H. A randomized placebo-controlled study of preoperative pregabalin for postoperative analgesia in patients with spinal surgery. [64]. 1. [70]. Spinal fusion; Pain; Analgesics; Pain treatment. Comparison of effects of hemostatic gelatin sponge impregnated with ropivacaine versus normal saline applied on the transverse process of the operated vertebrae on postoperative, [19]. Herein, we report the postoperative muscle changes measured using this formula. ketamine infusion, epidural analgesia, and i.t. [55]. Statistical calculations were performed using SPSS software, version 20.0 (IBM Corp., Armonk, NY, USA). Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Diagnostic imaging of spinal fusion and complications [33]. Imaging Features of Postoperative Complications After Spinal - AJR (50 mg, first choice) pentazocine hydrochloride (15 mg IM, second choice), 1: (n = 30) pregabalin 75 mg, 2 hours Prior to surgery. After a fusion retractor was applied, subtotal laminectomy with medial bilateral facetectomies were performed. Therefore, this systematic review aims to investigate whether the existing literature contains evidence concerning procedure-specific, medication-based interventions for 1- or 2-level spinal fusion surgery. Google Scholar. One trial reported on pruritus.68. Furthermore, we excluded trials dealing with spine surgery not related to spinal fusion, 409 trials were full-text screened, ending up with a total exclusion of 364 trials. suggested that when disc herniation compresses the spinal nerve, it also compresses the dorsal rami innervating the MF and ES, thereby causing muscle damage [16], and they asserted through the MF biopsy study that these muscle changes can be reversed by appropriate surgical treatment [16]. (2) Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. We contacted the corresponding author for the trial by email to confirm or obtain data if data were missing, or we classified bias evaluation as unclear in one or more domains. 4). JHC: analysis and interpretation of data. We declare that the study has been performed in accordance with the Declaration of Helsinki and has been approved by the institutional review board of Korea University Ansan Hospital (approval number: 2019AS0051). midazolam. Posterior lumbar fusion surgery negatively affected the regional vBMDs in adjacent levels. [24]. every 6 hours; during a period of 72 hours. [12]. Mengiardi B, Schmid MR, Boos N, Pfirrmann CW, Brunner F, Elfering A, et al. Freeman MD, Woodham MA, Woodham AW. [6]. morphine equivalents (Appendix 2, available at https://links.lww.com/PR9/A157) and pain scores, such as visual analog scale (VAS) 0 to 10 and numerical rating scale (NRS) 0 to 10, to a 0 to 100 VAS scale. Pain at the bone graft site. 2005;30(1):1239. However, most of the included studies represent an unclear or high risk of bias and low or very low quality of evidence. Imaging Features of Postoperative Complications After Spinal - AJR Brill S, Ginosar Y, Davidson EM. claimed that mini-open PLIF is preferable because injury of the medial MF of the paraspinal muscle is caused by direct injury from dissection or retraction [4]. 7-9). modify the keyword list to augment your search. Rantanen J, Hurme M, Falck B, Alaranta H, Nykvist F, Lehto M, et al. 2015;9:25. Anesthesiology 2020, 132:9921002. Three studies reported on this outcome.12,68,74 The meta-analysis favored the experimental group and showed a significant difference of 12 mm in overall effect mean VAS (95% CI: 617). Zhang Q, Wu Y, Ren F, Zhang X, Feng Y. We included RCTs comparing the postoperative effect of a perioperative analgesic intervention for 1- or 2-level spinal fusion surgery against a control group. Twenty-nine trials included patients with chronic pain and daily opioid consumption, 13 trials accepted pain but excluded preoperatively opioid consumption, 2 trials did not mention preoperatively pain or opioid consumption. 20 minutes before wound closure +2 mL/hr; fentanyl i.v. morphine.12,14,68,74 The risk of bias for all trials was low in one trial, unclear in 2 trials, and high in one trial (Fig. However, there are only limited data identifying the rate of instrumentation changes on radiographs after complex spine surgery involving 5-level fusions.METHODSThe medical records of 136 adult ( 18 years old) patients with spine deformity undergoing elective, primary complex spinal fusion ( 5 levels) for deformity correction at a . Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen V. Analgesic effect of intraoperative intravenous S-ketamine in opioid-naive patients after major lumbar fusion surgery is temporary and not dose-dependent: a randomized, double-blind, placebo-controlled clinical trial. Aglio LS, Abd-El-Barr MM, Orhurhu V, Kim GY, Zhou J, Gugino LD, Crossley LJ, Gosnell JL, Chi JH, Groff MW. 2c). 1996;5(3):1937. Such patients aged >18.1 years, with Cobb angles > 77, operation times > 430 min, and/or blood transfusion volume of > 1500 ml may be morphine. Correspondence to [69]. Three studies reported on this outcome.12,68,74 The meta-analysis favored the experimental group and showed a significant difference in the overall effect of 9 mm in mean VAS (95% CI: 315). Physical Therapy after a Spinal Fusion. [15]. Intra- and postoperative very low dose intravenous ketamine infusion does not increase, [65]. This formula is even more meaningful when considering the fact that in MRI, axial imaging is performed only at regions of interest and the angle of the cross-section is not constant. In one study, the patients had flurbiprofen at request. Sihvonen et al. Considering the stabilizing effect of the PLIF surgery, it is difficult to observe the correlation between muscle atrophy and LBP in the short term follow-up. 2 (a, b, c) revealed that the volumes of the MF and ES tended to decrease overall, while the volume of the psoas muscles tended to be unchanged, or even increased. Fifty-three patients (mean [95% confidence interval; CI] age = 59.2 [56.2, 62.3] years, 64% female) who underwent spine surgery for a degenerative lumbar condition were assessed at 6 weeks and 3 . Secondary endpoints were pain at rest and during mobilization at 6 and 24 hours postoperatively, opioid-related adverse effects, serious adverse events (SAEs), and length of stay (LOS). However, in 6 trials, the corresponding author had left no email address, and 7 email addresses were out of order. Lee JC, Cha JG, Kim Y, Kim YI, Shin BJ. ; end of surgery, 1: (n = 42) duramorph injection 0.011 mg/kg; 30 minutes before surgery, Indomethacin sup. In contrast, the BMI was not correlated with the changes in muscle volume in both the MRI and CT groups (Table4). Acta Anaesthesiol Scand 2014;58:118298. Changes in Paraspinal Muscles and Facet Joints after - Hindawi The formula for the volume measurement of the paraspinal muscles was used to calculate the volume through a simple measurement of the image, similar to the ABC / 2 formula used to measure the intracerebral hemorrhage volume. Greater than 3 of motion between flexion and extension views obtained 8-16 weeks after surgery is suggestive of failed fusion. GRADE Working Group grades of evidence: (1) High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. In particular, in atrophic muscle changes, size is reduced and fat deposits are increased [12, 22]. Eur Spine J. postoperatively; postop: PCA fentanyl (2 mL on demand) postoperatively + 25 mg meperidine i.v. 1 - 4 The three recognized causes of postoperative visual loss are ischaemic optic neuropathy, central retinal artery thrombosis and cortical blindness. For the comparison of the MRI group and the CT group, chi-square test was used for categorical variables and Student t-test or Mann-Whitney U test for continuous variables. You may search for similar articles that contain these same keywords or you may The quality of evidence (GRADE) was very low (Table 2). Kehlet H, Dahl JB. Recovery After Spinal Fusion: What to Expect - Healthgrades complications [13] (Figs. Fifteen trials reported that patients postoperatively were provided with patient-controlled analgesia with morphine, and in 6 cases, the morphine was solely administrated as i.v. Post-surgical inflammatory neuropathy | Brain | Oxford Academic [39]. The heterogeneity was moderate, I2 = 55% (Appendix 8, available at https://links.lww.com/PR9/A157). Aubrun F, Langeron O, Heitz D, Coriat P, Riou B. Randomised, placebo-controlled study of the postoperative analgesic effects of ketoprofen after, [4]. 4). However, the accuracy of the cross-section seems to be limited considering that the cross-section may not be uniform during MRI. Lumbosacral fusion increases the risk of hip osteoarthritis 2). . However, in South Korea, the cost of an MRI is 34 times that of a CT; therefore, there is a cost disadvantage for monitoring the muscle status with MRI, and the instrumentation may interfere with accurate muscle demarcation due to metallic artifacts. Perioperative visual loss after spine surgery - PMC Because pain data often per se is nonparametric, it was necessary to perform the meta-analysis by converting median (interquartile range) to mean (SD) values, which could have affected the data. We used sensitivity analyses to explore whether the choice of summary statistics and choices made through the review process, such as selection of event category, were critical for the conclusions of the meta-analysis. It was difficult to perform MRI follow-up after surgery in lower income patients, and CT could not be repeatedly performed if the patients did not consent to repeated exposure to radiation. Your message has been successfully sent to your colleague. Int J Spine Surg 2018;12:43440. Reuben SS, Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of celecoxib, pregabalin, and their combination for, [60]. The quality of evidence (GRADE) was moderate (Table 2). Preemptive analgesia after lumbar spine surgery by pregabalin and celecoxib: a prospective study. However, the nature of changes in postoperative paraspinal muscle after damage by lumbar fusion surgery has remained largely unknown. suggested the possibility of denervation-related atrophy in lumbosacral radiculopathy [11]. The heterogeneity was large, I2 = 91% (Fig. The quality of evidence (GRADE) was very low (Table 2). Similarly, the lower surface was measured at the upper endplate level of S1. Seven trials reported on ketamine as an intervention.1,5,24,41,53,64,66 The risk of bias for all trials was low in 2 trials, unclear in 2 trials, and high in 3 trials (Fig. Objective: To describe an objective method for evaluating changes in upper- and lower-extremity spasticity and strength, as well as temporal and kinematic gait variables, after surgical intervention for cervical spondylotic myelopathy. However, this procedure is known to have several disadvantages, one of which is the postoperative atrophy of the paraspinal muscles [2,3,4,5,6]. Modalities for symptom modulation if indicated Criteria for progression to next phase: Formal Therapy may begin 7-12 weeks post fusion according to patient clinical progress Pain and swelling within tolerance Independent with HEP Tolerates 15 min of exercise and 15-30 min of cardiovascular exercise As a result, we could have rated some of the studies too hard hereby, affecting the GRADE evaluation.