8. Herpes zoster and post herpetic neuralgia.

INTRODUCTION: Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person-years. In one out of four patients, acute HZ-related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN. METHODS: The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized. RESULTS: The most important treatment for acute HZ-related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. CONCLUSIONS: Treatment of acute HZ-related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management.

Pain and psychopathology after intensive care unit admission.

Pain and psychopathology are observed in 18% and 55% of patients, respectively, 1 year after intensive care unit (ICU) admission. It is well known that chronic pain and psychopathology have a bidirectional relation in the general population, but it is not known whether this holds true for ICU survivors. The aim of this study was to investigate whether pain before, during and after ICU admission is related to psychopathology in ICU survivors 1 year after discharge. We performed a cohort study in a mixed ICU in the Netherlands between 2013 and 2016. At 1-year follow-up, patients completed the Hospital Anxiety and Depression Scale, the Impact of Event Scale/Impact of Event Scale-Revised, and answered standardised questions regarding pain. Psychopathology was defined as having anxiety, depressive and/or post-traumatic stress disorder symptoms. We used multivariable logistic regression analysis to evaluate the association of pain before, during and after ICU admission with psychopathology at 1 year follow-up. We included 1105 patients of whom 558 (50%) (95% confidence interval (CI) 0.48 to 0.54) had psychopathology at 1 year follow-up. Pain before ICU admission (odds ratio (OR) 1.18; 95% CI 1.10 to 1.26) and pain after ICU admission (OR 2.38; 95% CI 1.68 to 3.35) were associated with psychopathology. Pain during ICU stay was not associated with psychopathology, but the memory of insufficient pain management during ICU stay was (OR 2.19; 95% CI 1.39 to 3.45). Paying attention to pain and pain treatment experiences related to ICU admission may therefore contribute to early identification of ICU survivors at risk of psychopathology development.

Multidisciplinary strategies to treat painful mononeuropathies in the upper extremity: from lab to bedside.

Neuropathic pain in the upper extremity is a serious problem, commonly involving relatively young patients. The pain causes loss of function and productivity, changes a patient's lifestyle and can progress into a chronic pain syndrome with secondary psychosocial co-morbidities. Treating patients with a painful mononeuropathy remains challenging, with a monodisciplinary approach often having limited treatment efficacy. This narrative review discusses how to deal with this challenge in the treatment of patients with peripheral nerve injury pain, addressing the four important pillars: (1) diagnosing a painful mononeuropathy; (2) clinical pain phenotyping; (3) personalized pain treatment; and (4) using a multidisciplinary team approach.

Cohort profile of PLUTO: a perioperative biobank focusing on prediction and early diagnosis of postoperative complications.

PURPOSE: Although elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies. PARTICIPANTS: Patients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens are collected at preselected time points. Primary study outcomes are the postoperative occurrence of nosocomial infections, major adverse cardiac events, pulmonary complications, acute kidney injury and delirium/acute encephalopathy. Secondary outcomes include mortality and quality of life, as well as the long-term occurrence of psychopathology, cognitive dysfunction and chronic pain. FINDINGS TO DATE: Enrolment of the first participant occurred early 2020. During the inception phase of the project (first 2 years), 431 patients were eligible of whom 297 patients consented to participate (69%). Observed event rate was 42% overall, with the most frequent complication being infection. FUTURE PLANS: The main purpose of the PLUTO biorepository is to provide a framework for research in the field of perioperative medicine and anaesthesiology, by storing high-quality clinical data and biomaterials for future studies. In addition, PLUTO aims to establish a logistical platform for conducting embedded clinical trials. TRIAL REGISTRATION NUMBER: NCT05331118.

Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study.

BACKGROUND: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. METHODS: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. RESULTS: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. CONCLUSIONS: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

Development and validation of a multivariable prediction model for early prediction of chronic postsurgical pain in adults: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of developing chronic postsurgical pain (CPSP) is an essential step in reducing pain chronification in postsurgical patients. We aimed to develop and validate a prognostic model for the early prediction of CPSP including pain characteristics indicating altered pain processing within 2 weeks after surgery. METHODS: A prospective cohort study was conducted in adult patients undergoing orthopaedic, vascular, trauma, or general surgery between 2018 and 2019. Multivariable logistic regression models for CPSP were developed using data from the University Medical Centre (UMC) Utrecht and validated in data from the Erasmus UMC Rotterdam, The Netherlands. RESULTS: In the development (n=344) and the validation (n=150) cohorts, 28.8% and 21.3% of patients reported CPSP. The best performing model (area under the curve=0.82; 95% confidence interval [CI], 0.76-0.87) included preoperative treatment with opioids (odds ratio [OR]=4.04; 95% CI, 2.13-7.70), bone surgery (OR=2.01; 95% CI, 1.10-3.67), numerical rating scale pain score on postoperative day 14 (OR=1.57; 95% CI, 1.34-1.83), and the presence of painful cold within the painful area 2 weeks after surgery (OR=4.85; 95% CI, 1.85-12.68). Predictive performance was confirmed by external validation. CONCLUSIONS: As only four easily obtainable predictors are necessary for reliable CPSP prediction, the models are useful for the clinician to be alerted to further assess and treat individual patients at risk. Identification of the presence of painful cold within 2 weeks after surgery as a strong predictor supports altered pain processing as an important contributor to CPSP development.

Postoperative Pain and Age: A Retrospective Cohort Association Study.

BACKGROUND: As the population ages, the number of elderly people undergoing surgery increases. Literature on the incidence and intensity of postoperative pain in the elderly is conflicting. This study examines associations between age and pain-related patient reported outcomes and perioperative pain management in a dataset of surgical patients undergoing four common surgeries: spinal surgery, hip or knee replacement, or laparoscopic cholecystectomy. Based on the authors' clinical experience, they hypothesize that pain scores are lower in older patients. METHODS: In this retrospective cohort, study data were collected between 2010 and 2018 as part of the international PAIN OUT program. Patients filled out the International Pain Outcomes Questionnaire on postoperative day 1. RESULTS: A total of 11,510 patients from 26 countries, 59% female, with a mean age of 62 yr, underwent one of the aforementioned types of surgery. Large variation was detected within each age group for worst pain, yet for each surgical procedure, mean scores decreased significantly with age (mean Numeric Rating Scale range, 6.3 to 7.3; ß = -0.2 per decade; P ≤ 0.001), representing a decrease of 1.3 Numeric Rating Scale points across a lifespan. The interference of pain with activities in bed, sleep, breathing deeply or coughing, nausea, drowsiness, anxiety, helplessness, opioid administration on the ward, and wish for more pain treatment also decreases with age for two or more of the procedures. Across the procedures, patients reported being in severe pain on postoperative day one 26 to 38% of the time, and pain interfered moderately to severely with movement. CONCLUSIONS: The authors' findings indicate that postoperative pain decreases with increasing age. The change is, however, small and of questionable clinical significance. Additionally, there are still too many patients, at any age, undergoing common surgeries who suffer from moderate to severe pain, which interferes with function, supporting the need for tailoring care to the individual patient.

Effectiveness of Epiduroscopy for Patients with Failed Back Surgery Syndrome: A Systematic Review and Meta-analysis.

INTRODUCTION: Low-back or leg pain in patients suffering from failed back surgery syndrome (FBSS) is often severe, having a major impact on functionality and quality of life. Despite conservative and surgical treatments, pain can be persistent. An alternative treatment option is epiduroscopy, a minimally invasive procedure based on mechanical adhesiolysis of epidural fibrosis. As epidural fibrosis is speculated to be a major contributor in the pathophysiologic process of FBSS, this review evaluates the effectiveness of epiduroscopy in FBSS patients. METHODS AND MATERIALS: A systematic literature search was performed in PubMed, Embase, and Cochrane databases. Critical appraisal was performed using validated tools. Meta-analysis was performed using generic inverse variance analysis. RESULTS: From the 286 identified articles, nine studies were included. The visual analogue scale (VAS) average was 7.6 at baseline, 4.5 at 6, and 4.3 at 12 months. The Oswestry Disability Index (ODI) average was 61.7% at baseline, 42.8% at 6, and 46.9% at 12 months. An average of 49% of patients experienced significant pain relief at 6 and 37% at 12 months. Meta-analysis showed a pooled VAS mean difference of 3.4 (2.6 to 4.1; 95% confidence interval [CI]) and 2.8 (1.6 to 4.0; 95% CI) and pooled ODI mean difference of 19.4% (12.5 to 26.4%; 95% CI) and 19.8% (13.8 to 25.9%; 95% CI) at 6 and 12 months, respectively. CONCLUSION: Current literature demonstrates a clinically relevant reduction in pain and disability scores at 6 to 12 months after mechanical adhesiolysis in FBSS patients. The quality of evidence is moderate, and the level of recommendation is weak. Practitioners should consider the benefits of epiduroscopy after weighing the risks for individual patients with FBSS.

Occurrence and Risk Factors of Chronic Pain After Critical Illness.

OBJECTIVES: Occurrence, risk factors, and impact on daily life of chronic pain after critical illness have not been systematically studied. DESIGN: Cohort study. SETTING: A tertiary ICU in The Netherlands. PATIENTS: We surveyed patients who had been discharged from our ICU between 2013 and 2016. Three cohorts were defined as follows: 1) ICU survivors; 2) one-year survivors reporting newly-acquired chronic pain; and (3) one-year survivors with pain who lived within 50 km from the study hospital. In cohort 1, we estimated the prevalence of new chronic pain 1 year after ICU discharge and constructed a prediction model for its occurrence incorporating three outcomes: death during follow-up, surviving without new pain, and surviving with newly-acquired pain. In cohort 2, we determined clinical features of pain and its impact on daily life. In cohort 3, we assessed the presence of neuropathic characteristics of pain. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The three cohorts contained 1,842, 160, and 42 patients, respectively. Estimated occurrence of new chronic pain was 17.7% (95% CI, 15.8-19.8%; n = 242) in 1-year survivors (n = 1,368). Median pain intensity on the numeric rating scale was 4 (interquartile range, 2-6) in the week before survey response, with impact being most evident on activities of daily living, social activities, and mobility. Neuropathic pain features were present in 50% (95% CI, 37-68%) of affected subjects. Among nine predictor variables included in a multinomial model, only female gender and days in ICU with hyperinflammation were associated with pain. CONCLUSIONS: Newly-acquired chronic pain is a frequent consequence of critical illness, and its impact on daily life of affected patients is substantial.

Opioid-related beliefs and prescription modalities for postoperative pain of Dutch and American physicians.

Aim: Opioid consumption and addiction are increasing worldwide, yet the USA stands out for its high addiction rates and opioid-related deaths. Considering that patient characteristics are comparable across western countries, physicians' prescribing modalities may influence opioid consumption. We conducted a pilot study to examine opioid-related beliefs and prescription habits of Dutch and American physicians. Methods & materials: A survey was administered to 488 physicians who routinely prescribe opioids for postoperative pain. Results: A total of 75 (16%) physicians responded to the survey. When deciding to prescribe opioids, Dutch physicians adopted a patient-guided approach, whereas most American doctors followed strict guidelines and protocols. Conclusion: This study identified significant differences between Dutch and American physicians' attitudes and prescribing modalities.

Measurement properties of instruments to assess pain in children and adolescents with cancer: a systematic review protocol.

BACKGROUND: Pain in children and adolescents with cancer has been identified as an area where many healthcare professionals seek guidance. This protocol details a systematic review whose aim is to explore current knowledge regarding measurement instruments to assess pain (and pain-related distress) in children and adolescents with cancer. After completion of the review, the information will be used in the development of a clinical practice guideline. METHODS: We will search four electronic databases (MEDLINE via PubMed, CINAHL, PsycINFO and HaPI). Additional relevant studies will be identified by reference checking and expert consultation. All citations will be screened independently by two reviewers in a three-step approach: first selection based on title, second selection based on abstract, third selection based on full-text. Studies in children and adolescents with cancer that aimed to evaluate the clinimetric properties of an existing pain measurement instrument or to develop a new pain measurement instrument and that include at least one relevant outcome (reliability, validity, responsiveness, interpretability, clinical utility) are eligible for inclusion. For all steps of evidence selection, a detailed list with eligibility criteria will be determined a priori. Data extraction and quality assessment of included studies (according to the COnsensus-based Standards for the selection of health Measurement INstruments, COSMIN criteria) will be conducted independently by two authors. DISCUSSION: This systematic review will provide an overview of the current literature regarding measurement instruments to assess pain in children and adolescents with cancer. This knowledge synthesis will be used to formulate recommendations for clinical practice. Also, by synthesizing existing evidence, knowledge gaps will be identified. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017072879.

Safe Use of Epidural Corticosteroid Injections: Recommendations of the WIP Benelux Work Group.

BACKGROUND: Epidural corticosteroid injections are used frequently worldwide in the treatment of radicular pain. Concerns have arisen involving rare major neurologic injuries after this treatment. Recommendations to prevent these complications have been published, but local implementation is not always feasible due to local circumstances, necessitating local recommendations based on literature review. METHODS: A work group of 4 stakeholder pain societies in Belgium, The Netherlands, and Luxembourg (Benelux) has reviewed the literature involving neurological complications after epidural corticosteroid injections and possible safety measures to prevent these major neurologic injuries. RESULTS: Twenty-six considerations and recommendations were selected by the work group. These involve the use of imaging, injection equipment particulate and nonparticulate corticosteroids, epidural approach, and maximal volume to be injected. CONCLUSION: Raising awareness about possible neurological complications and adoption of safety measures recommended by the work group aim at reducing the risks for these devastating events.

Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model.

BACKGROUND AND AIMS: Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats. METHODS: Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400µg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR. RESULTS: Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls. CONCLUSIONS: In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. IMPLICATIONS: Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.

Analgesic properties of intrathecal glucocorticoids in three well established preclinical pain models.

BACKGROUND AND AIMS: Glucocorticoids, a group of anti-inflammatory agents, are frequently administered in pain medicine. Of interest is the reported activity after intrathecal delivery in patients with neuropathic pain syndromes such as postherpetic neuralgia, though its efficacy is controversial. After the publication of two randomized clinical trials in postherpetic neuralgia patients treated with similar intrathecal methylprednisolone acetate (MPA) dosing regimes with conflicting results; one showing significant pain reduction (Kotani N, Kushikata T, Hashimoto H, Kimura F, Muraoka M, Yodono M, Asai M, Matsuki A: Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;23: 1514-9), the other increased pain sensations (Rijsdijk M, van Wijck AJ, Meulenhoff PC, Kavelaars A, van der Tweel I, Kalkman CJ: No beneficial effect of intrathecal methylprednisolone acetate in postherpetic neuralgia patients. Eur J Pain 2013;38: 175-200), we decided additional research was warranted. Present study sought to determine effects of intrathecally delivered methylprednisolone on pain-like behaviour and pain-associated markers in three well established rodent pain models: (1) intraplantar carrageenan, (2) intraplantar formalin, and (3) ligation of L5/L6 spinal nerves (SNL model). METHODS: Male rats with intrathecal catheters were examined for (1) tactile allodynia after unilateral hindpaw intraplantar carrageenan injection (2%), (2) flinching and subsequent long term tactile allodynia after unilateral hindpaw intraplantar formalin injection (2.5%) or (3) tactile allodynia after unilateral ligation of the L5 and L6 spinal nerves. Rats were treated with the maximum tolerable intrathecal dose of the soluble methylprednisolone sodium succinate (MP) or the particulate methylprednisolone acetate (MPA). Dorsal root ganglia and spinal cords were harvested for immunohistochemistry to assess markers of neuronal damage (ATF3) and glial activation (GFAP, Iba1). RESULTS: During dose finding, severe generalized allodynia was observed with high intrathecal doses of both MPA and MP in naive rats. MPA had no effect upon tactile allodynia after carrageenan. MP and MPA did not reverse tactile allodynia in the SNL model, and did not reduce flinching in the formalin model. MP and MPA prevented the delayed (7-day) tactile allodynia otherwise observed in the formalin-injected paw. Systemic MP or perineural MP or MPA did not reduce pain-like behaviour in the SNL model. No reduction of neuronal injury (ATF3) in the dorsal root ganglion or astrocyte activation (GFAP) in the spinal dorsal horn with intrathecal MP or MPA was observed. There was a decrease in microglial activation (Iba1) in the spinal dorsal horn with MPA after SNL. CONCLUSION: Severe generalized allodynia was observed after high intrathecal doses of MP and MPA in naive rats. No acute analgesic effects with intrathecal glucocorticoids were observed in three well established pain models. Only a late antiallodynic effect was present in the formalin model, 7 days after formalin injection and drug treatment. IMPLICATIONS: Our results do not support use of intrathecal methylprednisolone in the treatment of pain.

The effects of glucocorticoids on neuropathic pain: a review with emphasis on intrathecal methylprednisolone acetate delivery.

Methylprednisolone acetate (MPA) has a long history of use in the treatment of sciatic pain and other neuropathic pain syndromes. In several of these syndromes, MPA is administered in the epidural space. On a limited basis, MPA has also been injected intrathecally in patients suffering from postherpetic neuralgia and complex regional pain syndrome. The reports on efficacy of intrathecal administration of MPA in neuropathic pain patients are contradictory, and safety is debated. In this review, we broadly consider mechanisms whereby glucocorticoids exert their action on spinal cascades relevant to the pain arising after nerve injury and inflammation. We then focus on the characteristics of the actions of MPA in pharmacokinetics, efficacy, and safety when administered in the intrathecal space.

Safety assessment and pharmacokinetics of intrathecal methylprednisolone acetate in dogs.

BACKGROUND: Intrathecal methylprednisolone acetate (MPA) has been used in patients with chronic pain syndromes. Its safety has been debated after reports of adverse events. No systematic preclinical evaluation of MPA has been reported. In the current study, the acute and long-term effects of intrathecal MPA on dog spinal tissue was studied with the injectate reformulated to include minimal adjuvants. METHODS: Seventeen dogs were implanted with intrathecal catheters and randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel with the human protocols, dogs received four injections at 7-day intervals. Clinical observations and plasma methylprednisolone measurements were done before and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long-term) after the last injection, animals were sacrificed and spinal tissues harvested for histopathology. RESULTS: Other than a brief motor block, no adverse clinical event occurred in any animal. Group A (vehicle) showed minimal histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0), group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction increased significantly with increasing dose at long-term sacrifice (acute P = 0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was seen in any animal. CONCLUSION: These results, showing dose-dependent intrathecal inflammatory reactions at MPA doses and injectate concentrations comparable to those used in humans, indicate that the continued use of this modality in humans is not recommended.

Diagnostic threshold values of cerebral perfusion measured with computed tomography for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Early diagnosis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage is critical but difficult. We analyzed diagnostic threshold values of CT perfusion for use in detection of DCI in patients with subarachnoid hemorrhage. METHODS: We prospectively enrolled patients with subarachnoid hemorrhage with CT perfusion on admission and at time of clinical deterioration or after 1 week if no deterioration occurred. The gold standard was the clinical diagnosis of DCI based on all clinical, laboratory, and imaging data except CT perfusion. Patients with failed imaging (n=6) and other causes of deterioration (n=45) were excluded for the current study. We measured CT perfusion values, including cerebral blood volume, blood flow, mean transit time (MTT), and time to peak in predefined regions of interest and then compared absolute perfusion and perfusion asymmetry for patients with and without DCI. Diagnostic threshold values for DCI were evaluated and sensitivity and specificity calculated for optimal thresholds. RESULTS: Of 85 eligible patients with subarachnoid hemorrhage, 50 had DCI; 35 patients with no clinical deterioration comprised the reference group. Cerebral blood flow was significantly lower, MTT higher, and perfusion asymmetry larger in patients with DCI. We found that largest absolute MTT and the MTT difference between hemispheres were good diagnostic tests. Diagnostic threshold values with optimal sensitivity and specificity were an MTT of 5.9 seconds and an MTT difference of 1.1 second. CONCLUSIONS: Thresholds for absolute MTT values and between-hemisphere MTT differences on CT perfusion can distinguish between patients with delayed cerebral ischemia and clinically stable patients.