Epinephrine and norepinephrine in cardiopulmonary resuscitation. Effects on myocardial oxygen delivery and consumption.

Norepinephrine, an alpha 1,2-beta 1,2-adrenergic agonist, seems to be an alternative to epinephrine, an alpha 1,2-beta 1,2-agonist, for restoration of spontaneous circulation in VF. We therefore studied the effect of epinephrine and norepinephrine on MDO2 and MVO2 using OCCM after five minutes of cardiopulmonary arrest in 21 pigs. After OCCM of three minutes, seven animals each received placebo (controls) or epinephrine (45 micrograms/kg) or norepinephrine (45 micrograms/kg). All drugs were given blindly. At 90 seconds after epinephrine or norepinephrine, mean arterial blood pressure was significantly higher than in the control group. Prior to cardiac arrest, MBF, measured with radioactive microspheres, was 193 +/- 30 ml/min/100 g. During CPR but before drug administration, MBF was 51 +/- 23 in the control group, 71 +/- 10 in the group with epinephrine, and 74 +/- 11 ml/min/100 g in the group with norepinephrine. At 90 seconds after epinephrine, MBF increased to 126 +/- 18 and after norepinephrine to 107 +/- 30 ml/min/100 g (p less than 0.05). Compared to OCCM alone, MDO2 increased from 9.6 +/- 1.7 to 17.1 +/- 3.2 ml/min/100 g after epinephrine and from 9.4 +/- 1.8 to 13.6 +/- 4.2 ml/min/100 g after norepinephrine (p less than 0.05). There was an increase in MVO2 from 4.0 +/- 1.5 to 9.4 +/- 3.0 ml/min/100 g after epinephrine (p less than 0.05), whereas MVO2 increased only from 4.2 +/- 0.8 to 5.1 +/- 2.0 ml/min/100 g after norepinephrine. Because epinephrine led to a greater increase in MVO2 than norepinephrine, the myocardial oxygen ER remained unchanged. The oxygen requirements of the fibrillating heart seemed to be increased via beta 2-adrenergic stimulation. In both the control and epinephrine-treated groups, only three of the seven animals could be successfully resuscitated, whereas all of the animals in the group with norepinephrine survived the 15-minute period of observation. In this model, norepinephrine, in contrast to epinephrine, improves the balance between MDO2 and MVO2 and eases restoration of spontaneous circulation.

Comparison of epinephrine and dopamine during cardiopulmonary resuscitation.

The effectiveness of epinephrine and dopamine for restoring spontaneous circulation after asphyxial or fibrillatory cardiac arrest was compared using a porcine model. Asphyxial arrest: 7 animals received 45 micrograms/kg epinephrine, 7 animals 2.5 mg/kg dopamine, the remaining 7 animals received no drug treatment. All 7 animals given epinephrine could be resuscitated after 174 +/- 53 s, spontaneous circulation could be restored in only 3 of 7 animals given dopamine after 487 +/- 63 s and in none of the control animals could spontaneous circulation be established. Ventricular fibrillation: 7 animals were defibrillated without either mechanical measures or drug therapy. The following doses were given before defibrillation and after starting mechanical measures to separate groups of 7 animals each: 45 micrograms/kg epinephrine, 2.5 mg/kg dopamine, or no drug therapy. In the absence of either drug or mechanical measures and with mechanical measures only, spontaneous circulation could not be established in any of the cases. After administration of epinephrine, defibrillation and restoration of spontaneous circulation was achieved in 6 of 7 animals in 667 +/- 216 s, with dopamine, all the animals could be successfully resuscitated in the shorter time of 174 +/- 85 s. Epinephrine was found to be superior to dopamine in the treatment of asphyxial arrest whereas dopamine was found to be better in the management of ventricular fibrillation, probably by improving the balance between myocardial oxygen supply and demand.

Clinical experimental studies of postoperative infusion analgesia.

Thirty postoperative patients, after undergoing abdominal hysterectomy and standard general anesthesia, were randomly allocated to three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramide, or ketamine. The patients rated their pain on a 15-cm visual analog scale. Patients in group 1 received pentazocine. Mean dosage was 0.12 mg/kg/hr on the day of operation, 0.1 mg/kg/hr on the first postoperative day, and only 0.07 mg/kg/hr on the second postoperative day. Pentazocine blood levels averaged 50 micrograms/L. Patients in group 2 received piritramide. Mean dosage was 0.038 mg/kg/hr on the day of operation, 0.024 mg/kg/hr on the first postoperative day, and 0.019 mg/kg/hr on the second postoperative day. Blood levels of piritramide were not determined because no satisfactory assay is available. Patients in group 3 received ketamine. Mean dosage was 0.32 mg/kg/hr on the day of operation, 0.28 mg/kg/hr on the first postoperative day, and 0.29 mg/kg/hr on the second postoperative day. Ketamine blood levels ranged between 120 and 180 micrograms/L. None of the three analgesics caused any important hemodynamic or respiratory side effects. Pentazocine and piritramide were more effective analgesics than ketamine was. Ketamine also had a higher incidence of side effects.

The effect of epinephrine on hemodynamics, acid-base status and potassium during spontaneous circulation and cardiopulmonary resuscitation.

The effect of a bolus dose of epinephrine on hemodynamics, acid-base status and potassium during spontaneous circulation and cardiopulmonary resuscitation (CPR) was investigated in 24 pigs weighing 20-25 kg over a period of 10 min. In a study of 12 pigs in a stable hemodynamic condition, at the 1- and 2-min point after injection of epinephrine or saline the mean serum potassium concentration was significantly higher in the six animals given epinephrine (6.9 +/- 0.7 and 5.4 +/- 0.6 mmol/l, respectively) than in the six control animals (3.8 +/- 0.6 and 3.9 +/- 0.4 mmol/l, respectively). At the later points of observation (3, 4, 5 and 10 min after injection of either epinephrine or saline) no significant difference was found between the groups. Following 1 min of ventricular fibrillation 12 pigs were resuscitated by closed-chest CPR. Six of these animals received 45 micrograms/kg epinephrine (epinephrine group), the other six animals were given physiological saline (control group). Mean aortic diastolic pressure during the relaxation phase was significantly higher in the epinephrine group than in the control group. There was no difference in cardiac index or acid-base status between the groups. In the epinephrine group mean arterial serum potassium concentrations reached a peak value of 6.7 +/- 1.1 mmol/l at 3 min after injection, when they were significantly (P less than 0.05) higher than in the control group (4.4 +/- 0.5 mmol/l). At 5 and 10 min, the potassium levels sank to 5.9 +/- 0.9 and 5.6 +/- 0.8 mmol/l, respectively, in the epinephrine group, and were no longer significantly different from the control group.

The respiratory aspect of the treatment of brain injury associated with acute alcohol intoxication--results of an animal experiment.

The effects of spontaneous respiration and mechanical ventilation were examined by investigating the interaction between elevated intracranial pressure and alcohol intoxication. Ethanol (200 ml 48%) was infused in 11 young pigs with elevated cerebral pressure during mechanical ventilation (group 1), 7 young pigs with elevated cerebral pressure during spontaneous respiration (group 2), and 4 young pigs without elevated cerebral pressure during spontaneous respiration (group 3). While the behavior of intracranial pressure during mechanical ventilation in the animals from group 1 was inhomogeneous with a tendency to rise (29-34 mmHg), cerebral pressure (28-55 mmHg) increased drastically in the animals from group 2. This increase was associated with a sharp rise of Pa,CO2 (37.6-73.3 mmHg) and a decrease of Pa,O2 (74 mmHg to 13 mmHg). None of the animals in group 2 survived. Pa,CO2 also rose in alcoholized animals without elevated cerebral pressure (group 3) (41.9-63.9 mmHg); intracranial pressure, however, remained within the normal range. All animals in group 3 survived. Our findings indicate that elevated intracranial pressure and alcohol intoxication have a cumulative or potentiating effect on depression of the respiratory center. Respiratory depression can be prevented by mechanical ventilation and, therefore, a further rise of intracranial pressure generally avoided.

The early use of positive end expiratory pressure (PEEP) ventilation in emergency medicine, and some experiments on pigs.

The effects on near drowning of young pigs of positive end expiratory pressure and zero end expiratory pressure were studied. The arterial PO2 and blood gases were examined during recovery from near drowning and after haemorrhagic shock. The cardiovascular parameters were measured after shock. The findings were considered in relation to the use of positive and expiratory pressure in patients. It was recommended that it be only administered by experienced staff in hospitals, and should not exceed 10 mbars, while 5 mbar was adequate and avoided complications in most cases.

[The role of non-opioid analgesics in the management of postoperative pain.]. / Stellenwert der nichtopioidanalgetika in der behandlung postoperativer schmerzen.

At present, intramuscular application of opioids given on request is the most widespread form of postoperative analgesia. This method is widely recognized as often being inadequate, however. As advanced techniques of pain management, such as patient-controlled analgesia, are not generally available, the question arises as to whether non-opioid analgesics should routinely be used in order to improve this situation. A review of the literature indicates that apart from when used following abdominal surgery, in particular, operations on the biliary tract, non-steroidal anti-inflammatory drugs (NSAIDS) offer effective postoperative pain control. Following minor surgery, the quality of analgesia can be better than that achieved with the weak opioids. The discrepancy between biliary tract operations and all other forms of surgery raises the question whether in the former case pain may have been partly due to spasms of visceral smooth muscle and hence be less readily amenable to the action of NSAIDS. A potential problem with the perioperative use of NSAIDS is that they inhibit platelet aggregation. Apart from tonsillectomy, there are no reports of increased intra- or postoperative bleeding when these drugs have been used for minor surgery, and only isolated reports following major operations. Despite these results, it must be borne in mind that most studies have been carried out on patients of ASA groups I and II and that conclusions drawn from the literature are not necessarily representative for the elderly and for patients with organ failure. Alternative substances have received relatively little attention. Of these, the pyrazolone derivative, metamizol, may well prove to be of value for patients in whom the use of NSAIDS is contraindicated or relatively ineffective such as after biliary tract surgery.

The effect of ketamine on intracranial pressure during haemorrhagic shock under the conditions of both spontaneous breathing and controlled ventilation.

Seventeen piglets of both sexes, seven with O2/air-buprenorphine anaesthesia and controlled ventilation, and ten unanaesthetized animals with normal, spontaneous respiration, were used for the study. The intracranial pressure of both groups of animals was raised by insufflation of an epidural balloon and the arterial blood pressure was reduced to approximately 70% of the original value by controlled haemorrhage. 0.5 mg/kg body weight of ketamine was given intravenously, followed by a further dose of 2.0 mg/kg body weight of ketamine five minutes later. Both ketamine doses led to a significant rise in the intracranial pressure of those animals breathing spontaneously (31.8 mm Hg to 39.1 mm Hg). In contrast, the ventilated animals showed a significant reduction in intracranial pressure. No changes in arterial PCO2 were observed in this group, while those piglets breathing spontaneously had dangerous PCO2 rises. At both ketamine doses a significant correlation could be found between the PCO2 and the intracranial pressure.

Cardiopulmonary resuscitation with interposed abdominal compression after asphyxial or fibrillatory cardiac arrest in pigs.

The purpose of this study was to compare the efficacy of standard cardiopulmonary resuscitation and cardiopulmonary resuscitation with interposed abdominal compression for restoration of spontaneous circulation in an asphyxial and fibrillatory arrest model. Twenty-eight pigs weighing 19-27 kg were randomly allocated to two arrest groups. Each of these two groups was then subdivided into a treatment group and a control group resulting in four groups of seven pigs each. In the control groups standard cardiopulmonary resuscitation was performed with a pneumatically driven chest compressor at a rate of 80 beats per min. The animals' lungs were ventilated at a respiratory rate of 20 breaths per min independently of chest compression. In the treatment group, in addition to standard cardiopulmonary resuscitation, manual interposed abdominal compression was applied at the midabdomen in the second half of the relaxation phase using a blood pressure cuff to measure and standardize the compressions. Following asphyxial cardiac arrest of 3 min, none of the seven animals could be resuscitated with standard cardiopulmonary resuscitation, whereas all seven animals could be resuscitated with interposed abdominal compression and standard cardiopulmonary resuscitation after 240 +/- 84 s. Following fibrillatory cardiac arrest of 4 min, none of the seven animals that received standard cardiopulmonary resuscitation and countershocks could be resuscitated. In the group that received standard cardiopulmonary resuscitation and interposed abdominal compression spontaneous circulation was achieved in all animals in 244 +/- 117 s. End-diastolic arteriovenous pressure difference, which correlates with coronary blood flow, was significantly higher with interposed abdominal compression during resuscitation from both forms of cardiac arrest. The results of our study indicate that cardiopulmonary resuscitation with interposed abdominal compression in the second half of the relaxation phase improves diastolic arteriovenous pressure difference and resuscitation success in comparison with that following standard cardiopulmonary resuscitation. The use of interposed abdominal compression during basic cardiac life support should be investigated further in patients.

Comparison of different doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model.

Published results of dose-response effects of adrenergic drugs (epinephrine [E]) vary so much between studies because of differences in animal models and duration of ischemia before drug administration. In this investigation the effects of different doses of E on coronary perfusion pressure (CPP), left ventricular myocardial blood flow (MBF) and resuscitation success were compared during closed-chest cardiopulmonary resuscitation (CPR) after a 4-minute period of ventricular fibrillation in 28 pigs. MBF was measured during normal sinus rhythm using tracer microspheres. After 4 minutes of ventricular fibrillation CPR was performed with the use of a pneumatic piston compressor. After 4 minutes of mechanical measures only, the animals were randomly allocated into four groups of seven, receiving 0.015, 0.030, 0.045, and 0.090 mg/kg E intravenously respectively. MBF measurements were started 45 seconds after E administration; hemodynamic measurements after 90 seconds. Four minutes after the first administration, the same E dose was given before defibrillation. The CPP of animals given 0.015, 0.030, 0.045 and 0.090 mg/kg E were as follows: 16.3 +/- 6.1, 25.6 +/- 5.8, 33.2 +/- 8.4 and 30.4 +/- 6.3 mm Hg. The left ventricular MBF values were: 14 +/- 9, 27 +/- 11, 43 +/- 6, 46 +/- 10 mL/min/100 g. The differences between the groups receiving 0.015 and 0.045 mg/kg and between the groups receiving 0.015 mg/kg and 0.090 mg/kg were statistically significant (P less than .05). Resuscitation success was 14.3%, 42.9%, 100% and 86.7% respectively. A significant difference in resuscitation success was found only between 0.015 mg/kg and 0.045 mg/kg E.(ABSTRACT TRUNCATED AT 250 WORDS)

[The influence of heparin and dilution of the results of blood gas analyses (author's transl)]. / Einfluss bon Heparin und Verdünnung auf die Messwerte der Blutgasanalyse.

The results of blood gas analyses are affected by the type and length of storage of the sample and by differences in dilution and heparin concentration. Experiments established that keeping the specimen in iced water for one hour had no effect. Increasing the heparin concentration affected the results less than did dilution of the sample despite the acidity of the solution. If, on the other hand, heparin in powder form was employed (Monovette) the results were influenced by the absence of dilution of the sample and by the different type of heparin used. This particularly affected the acid-base balance and has to be taken into account when evaluating the results. The use of heparin Monovette simplifies the technique of taking blood samples as there is no need to fill the dead space and it provides reproducible results as the problem of differences in dilution does not arise.

Effects of epinephrine and norepinephrine on cerebral oxygen delivery and consumption during open-chest CPR.

The effect of epinephrine and norepinephrine on cerebral oxygen delivery and consumption after five minutes of cardiopulmonary arrest and three minutes of open-chest cardiac massage was studied in 21 pigs. Norepinephrine, like epinephrine, has a marked alpha- and beta 1-sympathomimetic activity, but compared with epinephrine, the degree of beta 2-stimulation is weak. Epinephrine probably stimulates cerebral oxygen and glucose consumption by its beta 2-adrenergic effect. After three minutes of CPR, three groups of seven animals each blindly received either placebo (control group), 45 micrograms/kg epinephrine, or 45 micrograms/kg norepinephrine. During CPR but before drug administration, cerebral blood flow was 23 +/- 14 mL/min/100 g in the control group, 30 +/- 7 mL/min/100 g in the epinephrine group, and 30 +/- 11 mL/min/100 g in the norepinephrine group. At 90 seconds after epinephrine, cerebral blood flow increased to 54 +/- 14 mL/min/100 g and after norepinephrine, to 58 +/- 22 mL/min/100 g (P less than .05). Cerebral perfusion pressure for both drugs was significantly higher than the control group. Compared with mechanical measures alone, cerebral oxygen delivery rose from 4.3 +/- 1.2 to 7.4 +/- 1.7 mL/min/100 g after epinephrine and from 3.7 +/- 1.4 to 7.3 +/- 2.7 mL/min/100 g after norepinephrine (P less than .05). There was no increase in cerebral oxygen consumption after both catecholamines, and cerebral oxygen extraction ratio decreased. Cerebral glucose delivery increased in relation to glucose consumption, and extraction ratio did not change significantly after both catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lidocaine levels in the plasma following peripheral or central venous administration during cardiopulmonary resuscitation. Results of an experimental animal study]. / Lidocainkonzentrationen im Plasma nach peripher- bzw. zentralvenöser Applikation während der kardiopulmonalen Reanimation. Ergebnisse einer tierexperimentellen Studie.

A review of the literature indicates that the intravenous bolus dose of lidocaine should be reduced in all conditions where cardiac output is diminished. During external cardiac compression the cardiac output is only approximately 20-40% of the normal resting value. Various routes of drug administration are currently used during CPR. The routine use of a central venous line is not recommended as a first-line procedure for resuscitation. This route of administration is favored by some authors, however, because it is presumed to result in a more rapid onset of drug action and higher peak concentrations of the drugs used. The aim of this study was to determine the aortic plasma concentration of lidocaine after central venous as compared to peripheral venous administration under the conditions of external cardiac compression. Twelve pigs were allocated to two groups of 6 animals each using random numbers. Ventricular fibrillation was induced by applying an alternating current via two needle electrodes placed subcutaneously. Cardiac arrest was allowed to continue for a period of 1 min before mechanical measures were applied. Cardiac massage was carried out using a pneumatic piston device set to a compression rate of 80/min. Sixty seconds after mechanical CPR had been initiated, a bolus of 1.5 mg/kg lidocaine was given to 6 animals via a central venous line. The remaining 6 animals were treated with the same dose given into a vein of the earlobe. The 2% lidocaine solution was diluted to 20 ml with physiological saline in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of epinephrine on systemic, myocardial, and cerebral acid-base status during cardiopulmonary resuscitation.

During cardiopulmonary resuscitation (CPR), arterial pH and carbon dioxide tension (PCO2) do not reflect the marked acidosis and hypercapnia seen in venous blood samples during CPR. Epinephrine causes an increase in myocardial and cerebral blood flow during CPR, but the influence on regional venous PCO2 and pH is as yet unknown. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 min of ventricular fibrillation and 3 min of open-chest CPR. Blood samples were obtained during CPR from the aorta, pulmonary artery, great cardiac vein, and sagittal sinus before and 90 s and 5 min after drug administration. Regional blood flow was measured with tracer microspheres. Plasma catecholamines were quantified by high-performance liquid chromatography in arterial blood. PCO2 90 s after drug administration in arterial, mixed venous, myocardial venous, and cerebral venous blood were (means +/- SD) 36 +/- 8, 67 +/- 9, 74 +/- 14, and 79 +/- 19 mmHg in the control group and 35 +/- 11, 62 +/- 12, 73 +/- 10, and 71 +/- 14 mmHg in the epinephrine group. pH values 90 s after drug administration in the same blood samples were 7.29 +/- 0.11, 7.11 +/- 0.09, 7.04 +/- 0.09, and 7.07 +/- 0.10 in the control group and 7.31 +/- 0.13, 7.17 +/- 0.07, 7.08 +/- 0.08, and 7.07 +/- 0.12 in the epinephrine group. Despite a significant increase in myocardial and cerebral blood flow after epinephrine, PCO2 and pH in all blood samples were not different from those of the control group. (ABSTRACT TRUNCATED AT 250 WORDS)

Investigation of intrapartum clearance of the upper airway in the presence of meconium contaminated amniotic fluid using an animal model.

In order to define as effective a procedure as possible for the intra- and post-partum clearance of the upper airways of meconium contaminated infants, three methods of suction clearance, nasal, oral and combined nasal and oral, were carried out on each of five kittens aged between 17 to 19 weeks. There was an interval of at least one week between each investigation. The animals were anaesthetized with ketamine intramuscularly. The pressure changes during delivery were simulated using a compressed blood pressure cuff around the kittens thorax. During the first minute of thoracic compression Tc 99 labeled synthetic sputum was introduced into both the oro- and nasopharynx, then during the 2nd minute the instilled fluid was removed using a conventional extractor with mucus trap. Solely oral or solely nasal routes were used, suction was carried out for 60 secs, whereas when the combined technique was applied the oral and nasal cavities were cleared for only 30 secs each. At the end at the 2nd minute thoracic compression was released and a deep inspiration occurred. After five minutes the radioactivity remaining after suction was documented using a gamma-camera. We attempted to answer the following questions: How much mucus could be extracted with each different method, and where the remaining amount was later distributed? Nasal suction alone was found to be inefficient; using this route an average of 13% (only an eight of the amount instilled) could be removed. Oral suction led to the recovery of an average of 52% of the material instilled, the combined technique much as 56%. After re-establishment of spontaneous respiration, it could be clearly seen that, independent of the efficacy of the technique used, the majority of the remaining radioactivity (55 relative percent) is localized in the head and neck area. Absolute values are 45% for nasal suction, 26% for oral, and 24% for the combined oro-nasal route. The other part of the remaining radioactivity was found in the lung or in the stomach. It must be pointed out that the aspirate need not be disturbed in both of the parts, both the stomach and the lungs can be solely involved. Five minutes after spontaneous respiration had been resumed the lungs revealed only a centrally distributed radioactivity. This corresponds anatomically to the trachea and major bronchi. The peripheral area of the lungs was free of aspirate at this point in time.(ABSTRACT TRUNCATED AT 400 WORDS)

[Comparative studies on the side effects of morphine after peridural, spinal and intravenous administration]. / Vergleichende Untersuchungen der Nebenwirkungen von Morphin nach periduraler, spinaler und intravenöser Applikation.

A prospective randomized study was carried out on 29 patients undergoing transurethral prostatectomy. In addition to the regional anaesthetic given for the operation, the patients received either: 1 mg morphine intrathecally (spinal group), 0.05 mg/kg body weight of morphine i.v. (i.v. group), or 0.05 mg/kg body weight epidurally (PDA group). Two of the intrathecal group patients had to be given an antagonist because of clinically relevant respiratory depression. In one of these cases, this depression could be documented by a continuous fall in respiratory minute volume, and an increase in PCO2. In the other, bradypnoea and vomiting developed within a few minutes of injection. The presence of a central action of intrathecal and epidural opiates was indicated by the significant increase in reaction time found. In the two instances of respiratory depression, the CSF morphine concentration 24 hrs after injection was markedly lower (0 and 18 ng/ml respectively) than in unaffected patients. It must therefore be assumed that the respiratory depression was caused by a more rapid cephelad transport than that occurring in normal cases.

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.