Prediction of postoperative pain from assessment of pain induced by venous cannulation and propofol infusion.

BACKGROUND: Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. METHODS: This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. RESULTS: Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). CONCLUSION: Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain.

Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion.

BACKGROUND: Thrombolysis is a common treatment for acute leg ischaemia. The purpose of this study was to evaluate different thrombolytic treatment strategies, and risk factors for complications. METHODS: This was a retrospective analysis of prospective databases from two vascular centres. One centre used a higher dose of heparin and recombinant tissue plasminogen activator (rtPA). RESULTS: Some 749 procedures in 644 patients of median age 73 years were studied; 353 (47·1 per cent) of the procedures were done in women. The aetiology of ischaemia was graft occlusion in 38·8 per cent, acute arterial thrombosis in 32·2 per cent, embolus in 22·3 per cent and popliteal aneurysm in 6·7 per cent. Concomitant heparin infusion was used in 63·2 per cent. The mean dose of rtPA administered was 21·0 mg, with a mean duration of 25·2 h. Technical success was achieved in 80·2 per cent. Major amputation and death within 30 days occurred in 13·1 and 4·4 per cent respectively. Bleeding complications occurred in 227 treatments (30·3 per cent). Blood transfusion was needed in 104 (13·9 per cent). Three patients (0·4 per cent of procedures) had intracranial bleeding; all were fatal. Amputation-free survival was 83·6 per cent at 30 days at both centres. In multivariable analysis, preoperative severe ischaemia with motor deficit was the only independent risk factor for major bleeding (odds ratio (OR) 2·98; P <0·001). Independent risk factors for fasciotomy were severe ischaemia (OR 2·94) and centre (OR 6·50). Embolic occlusion was protective for major amputation at less than 30 days (OR 0·30; P = 0·003). Independent risk factors for death within 30 days were cerebrovascular disease (OR 3·82) and renal insufficiency (OR 3·86). CONCLUSION: Both treatment strategies were successful in achieving revascularization with acceptable complication rates. Continuous heparin infusion during intra-arterial thrombolysis appeared to offer no advantage.

Clinical guidelines on central venous catheterisation. Swedish Society of Anaesthesiology and Intensive Care Medicine.

Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence-Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow-up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide-bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long-term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long-term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator-assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow-up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.

Survey of central venous catheterisation practice in Sweden.

BACKGROUND: Clinical guidelines on central venous catheterisation were introduced by the Swedish Society of Anaesthesiology and Intensive Care Medicine in 2011. The purpose of this study was to investigate current national practice and assess to what extent these guidelines influence clinical routines in Swedish operating wards and intensive care units. METHODS: An invitation to participate in an online survey regarding central venous catheterisation was sent to 65 departments of anaesthesiology and intensive care medicine in Sweden. The survey aimed at investigating routine standards (part 1) and 24-h clinical practice (part 2). RESULTS: Forty-seven (72%) and 49 (75%) of 65 departments took part in parts 1 and 2, respectively, and 73% adhered to the national guidelines. Many units monitored mechanical (42%) and infectious (69%) complications. Ultrasound was used by more than 50%. Checklists for insertion were used by 22%. Physicians inserted most catheters. No serious complications were reported during the 24-h study period. Ninety-seven non-tunnelled, 17 venous ports, 9 tunnelled and 8 peripheral central venous catheters were inserted. Ninety-three (71%) catheters were inserted in operating rooms, and 31 (24%) in intensive care units. Catheterisations were followed up by chest X-ray in most departments. CONCLUSION: Knowledge of the Swedish guidelines was adequate, and most participating departments had local catheterisation routines. We could identify some variation in practice, but overall adherence to the guidelines was good. Nevertheless, monitoring of procedures and complications of cannulation and maintenance could be in need of improvement.

Morning conferences for anaesthesiologists - to be or not to be?

BACKGROUND: The main objectives of this study were to clarify the contents of and attitudes to morning conferences for physicians at Swedish departments of anaesthesiology and intensive care medicine. METHODS: A prospective cross-sectional three-part study was carried out. Heads of departments responded to a national survey on the structure and content of morning conferences. A questionnaire on attitudes to and general contents of morning conferences was filled out by anaesthesiologists in the Scania region in southern Sweden. Furthermore, telephone interviews were made with anaesthesiologists on primary night call in the Scania region to obtain information on whether their needs to report had been met and on how the conferences had actually been carried out and attended by the physicians. RESULTS: Information was obtained from 52 departmental heads (80%), 113 anaesthesiologists (53%), and 83 physicians on primary call (92%). Issues most frequently brought up were reports from physicians on night call, discussions of clinical matters, issues of staffing, and organizational matters. Daily morning conferences were strongly favoured for intercollegial solidarity and contacts, and were mainly and regularly used for reports from physicians on night call. At 95% of them, physicians on night call considered themselves to have been allowed to report what they wanted or needed to. CONCLUSIONS: Daily morning conferences enable regular exchange of information and professional experience, and are considered by Swedish anaesthesiologists to be most valuable for intercollegial solidarity and contacts. Before changes are being made in frequency or duration of morning conferences, their actual structure and content should be carefully evaluated and critically challenged to fit specific needs of that individual department.

Complications associated with peripheral or central routes for central venous cannulation.

We undertook a review of studies comparing complications of centrally or peripherally inserted central venous catheters. Twelve studies were included. Catheter tip malpositioning (9.3% vs 3.4%, p = 0.0007), thrombophlebitis (78 vs 7.5 per 10,000 indwelling days, p = 0.0001) and catheter dysfunction (78 vs 14 per 10,000 indwelling days, p = 0.04) were more common with peripherally inserted catheters than with central catheter placement, respectively. There was no difference in infection rates. We found that the risks of tip malpositioning, thrombophlebitis and catheter dysfunction favour clinical use of centrally placed catheters instead of peripherally inserted central catheters, and that the two catheter types do not differ with respect to catheter-related infection rates.

Fluid balance monitoring by cuff-occluded rate of rise of peripheral venous pressure in haemodialysis patients.

Cuff-occluded rate of rise of peripheral venous pressure has been proposed to reflect volume changes in experimental studies. The aim of this study was to evaluate changes in cuff-occluded rate of rise of peripheral venous pressure associated with fluid removal by haemodialysis in six adult patients with chronic renal failure on intermittent haemodialysis. Measurements were carried out before and after each haemodialysis session. The volume of fluid removed (indexed to body surface area) linearly correlated with changes in cuff-occluded rate of rise of peripheral venous pressure (r = 0.84; r(2) = 0.70; p = 0.037). Cuff-occluded rate of rise of peripheral venous pressure may be feasible for future clinical monitoring of individual fluid balance.

Risk factors for haemorrhage during local intra-arterial thrombolysis for lower limb ischaemia.

Assessment of clinical risk factors for haemorrhagic complications in patients undergoing intra-arterial thrombolysis for lower limb ischaemia. Retrospective reviews of consecutive patients subjected to intra-arterial thrombolysis due to lower limb ischemia at the Vascular Center, Malmö University Hospital, during a 5-year period from 2001 to 2005. Two hundred and twenty intra-arterial thrombolytic procedures were carried out in 195 patients (46% women), median age 73 years. Haemorrhagic complications were recorded in 72 procedures (33%), of which 13 were discontinued. Haemorrhage at the introducer and distant sites occurred in 53 and 32 procedures, respectively. Thrombolysis for occluded synthetic grafts was associated with higher risk of haemorrhage (P = 0.043). The platelet count was lower (P = 0.017) and the dose of alteplas higher (P = 0.041) in bleeders than in non-bleeders. Age was not associated with haemorrhage (P = 0.30). Two patients died during thrombolysis, one of them due to intracerebral haemorrhage. The grade of thrombolysis was an independent predictor of both in-hospital amputation (P < 0.001; OR 3.5 [95% CI 2.1-5.8]) and mortality (P = 0.021; OR 3.0 [95% CI 1.2-7.9]). The in-hospital amputation-free survival rate was 85% (188/220). Haemorrhage associated with thrombolysis is common, but does seldom require discontinuation of treatment. Insertion of introducers for local thrombolysis through synthetic grafts, lower platelet count and higher alteplas dose were found to be risk factors for haemorrhage. An algorithm for clinical management of haemorrhage has been proposed.

Management of inadvertent arterial catheterisation associated with central venous access procedures.

OBJECTIVE: This study aims to describe the clinical management of inadvertent arterial catheterisation after attempted central venous catheterisation. METHODS: Patients referred for surgical or endovascular management for inadvertent arterial catheterisation during a 5-year period were identified from an endovascular database, providing prospective information on techniques and outcome. The corresponding patient records and radiographic reports were analysed retrospectively. RESULTS: Eleven inadvertent arterial (four common carotid, six subclavian and one femoral) catheterisations had been carried out in 10 patients. Risk factors were obesity (n=2), short neck (n=1) and emergency procedure (n=4). All central venous access procedures but one had been made using external landmark techniques. The techniques used were stent-graft placement (n=6), percutaneous suture device (n=2), external compression after angiography (n=1), balloon occlusion and open repair (n=1) and open repair after failure of percutaneous suture device (n=1). There were no procedure-related complications within a median follow-up period of 16 months. CONCLUSIONS: Inadvertent arterial catheterisation during central venous cannulation is associated with obesity, emergency puncture and lack of ultrasonic guidance and should be suspected on retrograde/pulsatile catheter flow or local haematoma. If arterial catheterisation is recognised, the catheter should be left in place and the patient be referred for percutaneous/endovascular or surgical management.

Routine chest X-ray is not required after a low-risk central venous cannulation.

BACKGROUND: Knowledge of the radiographic catheter tip position after central venous cannulation is normally not required for short-term catheter use. Detection of a possible iatrogenic pneumothorax may nevertheless justify routine post-procedure chest X-ray. Our aim was to design a clinical decision rule to select patients for radiographic evaluation after central venous cannulation. METHODS: A total of 2230 catheterizations performed using external jugular, internal jugular or subclavian venous approaches during a 4-year period were included consecutively. Information on patient data and corresponding procedures was recorded prospectively. A post-procedure chest X-ray was obtained after each cannulation. RESULTS: Thirteen cases (0.58%) of cannulation-associated pneumothorax were identified. The risk of pneumothorax after a technically difficult (1.8%) or subclavian (1.6%) cannulation was significantly higher than after cannulation not considered as difficult (0.37%) or performed using other routes (0.33%). Clinical signs of pneumothorax within 8 h of cannulation were found in all seven patients with pneumothorax requiring specific treatment. A new clinical decision rule for radiographic evaluation after central venous cannulation based on the results of the present study shows that 48% of the post-procedure chest X-rays performed in our patients were clinically redundant. CONCLUSION: Clinical symptoms were reported in all patients with pneumothorax requiring specific treatment. Approximately half of the post-procedure chest X-ray controls could be avoided using the proposed clinical decision rule to select patients for radiographic evaluation after central venous cannulation. A large prospective multi-centre study should be carried out to further evaluate this decision rule.

Racemic, S(+)- and R(-)-ketamine do not increase elevated intracranial pressure.

BACKGROUND: There is controversy regarding the influence of ketamine and its enantiomers on cerebral haemodynamics at increased intracranial pressure (ICP). This study was designed to compare cerebrovascular responses, with particular respect to ICP, to bolus injections of racemic, S(+)- and R(-)-ketamine in an experimental model of intracranial hypertension. METHODS: Nine pigs were anaesthetised with fentanyl and vecuronium during mechanical normoventilation. The ICP was raised with extradural balloon catheters to 23 mmHg. The intra-arterial xenon clearance technique was used to determine cerebral blood flow (CBF). Three 60-s bolus injections of racemic ketamine (10 mg/kg), S-ketamine (5 mg/kg) and R-ketamine (20 mg/kg) were given in a randomised sequence. Cerebral and systemic haemodynamic responses were evaluated before and at 1, 5, 10, 15, 30 and 45 min after each injection. RESULTS: Racemic ketamine decreased ICP (P=0.026) by maximally 10.8%, whereas there was no effect on ICP of S- (P=0.178) or R-ketamine (P=0.15). All study drugs had similar biphasic effects on CBF, with maximal initial decreases by 25-29%, followed by transient increases by 7-15%, and a reduction of mean arterial pressure by maximally 22-37%. CONCLUSIONS: A decrease or a lack of an increase in ICP in response to intravenous bolus injections of racemic, S- or R-ketamine suggests that the administration of racemic or S-ketamine might be safe in patients with intracranial hypertension due to a space-occupying lesion. The ICP-lowering effect indicates that racemic ketamine might offer a therapeutic advantage over S-ketamine.

Cerebral uptake of morphine in the pig calculated from arterio-venous plasma concentration gradients: an alternative to tissue microdialysis.

The aim of this study was to characterize the reversible cerebral uptake of morphine in the pig by measuring the changing arterio-venous plasma concentration gradient over the brain. Seven pigs were anaesthetized by continuous infusions of ketamine and pancuronium and ventilated with oxygen in nitrous oxide. During and after 5-min intravenous infusions of morphine hydrochloride, blood samples were drawn from a central artery and from the internal jugular vein. Concomitantly, cerebral blood flow (CBF) was repeatedly measured as clearance of 133Xe from the brain after intracarotid injection. Plasma concentrations of morphine and, in samples from two animals, morphine glucuronides were assayed by high-performance liquid chromatography. Drug flux (Jnet) from arterial blood to brain was calculated from the arterio-venous plasma concentration gradients, the blood:plasma concentration ratio and CBF. Uptake of morphine from arterial blood to brain was very rapid, with a maximal Jnet typically at 3 min after the beginning of the infusion. The initial cerebral extraction of morphine was close to 50%. When the arterial and jugular venous concentration curves crossed, 1-5 min after the end of the infusion, the initially rapid uptake of morphine changed into a slow and steady release. The cerebral extraction of morphine glucuronides was comparable to that of morphine, however, Jnet was lower due to lower plasma concentrations at time of maximal extraction. The findings demonstrate how the cerebral uptake and release of morphine and its metabolites can be studied with a method that is entirely non-invasive to the brain and permits very flexible sampling. Uptake and release of drug is observed directly and need not be inferred from cerebral concentration curves.

Cerebral blood flow at 0.5 and 1.0 minimal alveolar concentrations of desflurane or sevoflurane compared with isoflurane in normoventilated pigs.

Whether desflurane and sevoflurane have clinical advantages over isoflurane in neuroanesthesia is much debated. A porcine model was used for comparison of desflurane and sevoflurane with isoflurane with respect to their cerebrovascular effects. The minimal alveolar concentration (MAC) of each of the three agents was first determined in a standardized manner in six domestic juvenile pigs to enhance comparison reliability. Six other pigs were then anesthetized with isoflurane, desflurane, and sevoflurane, given in sequence to each pig in an even crosswise order with the first agent also used to maintain anesthesia during surgical preparation. Cerebral blood flow (CBF) was calculated from the clearance curve of intraarterially injected 133Xe. The mean arterial pressure (MAP) was invasively monitored. The estimated cerebrovascular resistance (CVRe) was calculated by dividing MAP with CBF, thereby approximating the cerebral perfusion pressure with MAP. For both MAC levels, the trend for CBF was desflurane > isoflurane > sevoflurane, and the trend for MAP and CVRe was sevoflurane > isoflurane > desflurane. Statistical comparison of desflurane and sevoflurane with isoflurane with respect to CBF and MAP revealed two statistically significant differences-namely, that CBF at 1.0 MAC desflurane was 17% higher than CBF at 1.0 MAC isoflurane (P =.0025) and that MAP at 1.0 MAC sevoflurane was 16% higher than MAP at 1.0 MAC isoflurane (P =.011). Consequently, in this study at normocapnia, these agents did not seem to differ much in their cerebral vasodilating effects at lower doses. At higher doses, however, desflurane, in contrast to sevoflurane, was found to induce more cerebral vasodilation than isoflurane.

Desflurane increases intracranial pressure more and sevoflurane less than isoflurane in pigs subjected to intracranial hypertension.

Desflurane and sevoflurane may have advantages over isoflurane in neuroanesthesia, but this is still under debate. A porcine model with experimental intracranial hypertension was used for paired comparison of desflurane, sevoflurane, and isoflurane with respect to the effects on cerebral blood flow (CBF), cerebrovascular resistance (CVR), and intracranial pressure (ICP). The agents, given in sequence to each of six pigs, were compared at 0.5 and 1.0 minimal alveolar concentrations (MAC) and three mean arterial blood pressure (MAP) levels (50, 70, and 90 mm Hg) at normocapnia and one MAP level (70 mm Hg) at hypocapnia. MAC for each agent had been previously determined in a standardized manner for comparison reliability. CBF was measured with Xe. MAP was lowered by inflation of a balloon catheter in the inferior caval vein and raised by inflation of a balloon catheter in the descending aorta. ICP was measured intraparenchymally. Two Fogarty catheters positioned extradurally were inflated to a baseline ICP of 20 to 22 mm Hg at 0.2 MAC of each agent. CBF and ICP with the three agents at normocapnia and MAP 70 and 90 mm Hg at both 0.5 and 1.0 MAC were as follows (P < 0.05): desflurane > isoflurane > sevoflurane. None of the agents abolished CO2 reactivity. High-dose desflurane resulted in a higher CBF at hypocapnia than corresponding doses of sevoflurane or isoflurane, but there were no significant differences between the agents in ICP at hypocapnia. The present study showed that desflurane increased ICP more and sevoflurane less than isoflurane during normoventilation, but the differences disappeared with hyperventilation.

Acupuncture for pain relief during childbirth.

BACKGROUND: There are few studies on acupuncture in childbirth despite the generally established analgesic effect of acupuncture treatment. METHODS: The analgesic effect of acupuncture during childbirth was assessed by comparing the need for other pain treatments (epidural analgesia using bupivacaine, pudendal nerve block, intramuscular meperidine, nitrous oxide/oxygen, intracutaneous sterile water injections) in 90 women given acupuncture (acupuncture group) with that in 90 women not given acupuncture (control group). RESULTS: 52 women (58%) in the acupuncture group and 13 (14%) in the control group managed their deliveries without further pain treatment (p < 0.001). The groups were similar with respect to age, pariety, duration of delivery, use of oxytocine and incidence of Caesarean section. Acupuncture treatment was found to have no major side effects, and 85 women (94%) given acupuncture reported that they would reconsider acupuncture in future deliveries. CONCLUSION: Acupuncture reduces the need for other methods of analgesia in childbirth.

[Ingestion of aliphatic hydrocarbons can cause life-threatening lung damage in infants]. / Aspiration av alifatiska kolväten kan ge livshotande lungpåverkan hos småbarn.

Ingestion of aliphatic hydrocarbons--even in small amounts--can cause severe respiratory distress in children. Such accidents are becoming increasingly common in Sweden. A case of severe hydrocarbon ingestion is reported, where a 16-month-old boy, initially treated with mechanical ventilation for respiratory distress, subsequently developed a reversible radiological complication, pneumatocele. Patients at risk of severe hydrocarbon intoxication can be identified by careful evaluation of their history and continuous clinical observation. Controlled ventilation should be instituted early in respiratory distress, and any radiological changes followed up in a few weeks.

The incidence and risk of central venous catheter malpositioning: a prospective cohort study in 1619 patients.

Central venous catheters are used in various hospital wards. An anterior-posterior chest X-ray is usually obtained soon after cannulation to assess the location of the catheter tip. This prospective clinical study was designed to determine the radiographic catheter tip position after central venous cannulation by various routes, to identify clinical problems possibly associated with the use of malpositioned catheters and to make a cost-benefit analysis of routine chest X-ray with respect to catheter malposition. A total 1619 central venous cannulations were recorded during a three-year period with respect to patient data, information about the cannulation procedures, the radiographic catheter positions and complications during clinical use. The total incidence of radiographic catheter tip malposition, defined as extrathoracic or ventricular positioning, was 3.3% (confidence interval 25 to 4.3%). Cannulation by the right subclavian vein was associated with the highest risk of malposition, 9.1%, compared with 1.4% by the right internal jugular vein. Six of the 53 malpositioned catheters were removed or adjusted. No case of malposition was associated with vascular perforation, local venous thrombosis or cerebral symptoms. We conclude that the radiographic incidence of central venous catheter malpositioning is low and that clinical use of malpositioned catheters is associated with few complications. However, determination of the catheter position by chest X-ray should be considered when mechanical complications cannot be excluded, aspiration of venous blood is not possible, or the catheter is intended for central venous pressure monitoring, high flow use or infusion of local irritant drugs.

Application of software design principles and debugging methods to an analgesia prescription reduces risk of severe injury from medical use of opioids.

A prescription is a health-care program implemented by a physician or other qualified practitioner in the form of instructions that govern the plan of care for an individual patient. Although the algorithmic nature of prescriptions is axiomatic, this insight has not been applied systematically to medication safety. We used software design principles and debugging methods to create a "Patient-oriented Prescription for Analgesia" (POPA), assessed the rate and extent of adoption of POPA by physicians, and conducted a statistical process control clinical trial and a subsidiary cohort analysis to evaluate whether POPA would reduce the rate of severe and fatal opioid-associated adverse drug events (ADEs). We conducted the study in a population of 153,260 hospitalized adults, 50,576 (33%) of whom received parenteral opioids. Hospitalwide, the use of POPA increased to 62% of opioid prescriptions (diffusion half-life = 98 days), while opioid-associated severe/fatal ADEs fell from an initial peak of seven per month to zero per month during the final 6 months (P < 0.0016) of the study. In the nested orthopedics subcohort, the use of POPA increased the practice of recording pain scores (94% vs. 72%, P < 0.00001) and the use of adjuvant analgesics (95% vs. 40%, P < 0.00001) and resulted in fewer opioid-associated severe ADEs than routine patient-controlled analgesia (PCA) (0% vs. 2.7%, number needed to treat (NNT) = 35, P < 0.015). The widespread diffusion of POPA was associated with a substantial hospitalwide decline in opioid-associated severe/fatal ADEs.