© U.S. Cancer Pain Relief Committee, 2002 0885-3924/02/$–see front matterPublished by Elsevier, New York, New York PII S0885-3924(02)00421-9

Vol. 24 No. 1 July 2002 Journal of Pain and Symptom Management 45

Original Article

Introduction

The majority of cancer patients experiencemoderate or severe chronic pain during thecourse of their illness.

1

Cancer pain is presentin 30–40% of patients at the time of diagnosis,and in about 75% of patients with advanced ill-ness. Adequate pain control can be obtained in

the majority of cancer patients. A standard pal-liative care practice is to prescribe an analgesicregimen for the persistent pain and then a sup-plemental on-demand dose for breakthroughpain.

1–3

Breakthrough pain (BTP), defined as a tran-sitory exacerbation of pain that is superim-posed on persistent stabilized chronic pain,

2

has been associated with a low probability ofadequate pain control in some groups of can-cer patients.

4

BTP characteristically has a quickonset (less than 3 minutes), a severe intensitybut brief duration (average of 30 minutes),and an average occurrence of 4 episodes a

Address reprint requests to:

Xavier Gómez-Batiste, MD,Servei de Cures Palliatives, Institut Català d’Oncolo-gia, Av. Gran Vía s/n, km 2,7, 08907 L’Hospitalet,Barcelona, Spain.

Accepted for publication: October 5, 2001.

Breakthrough Cancer Pain: Prevalence and Characteristics in Patients in Catalonia, Spain

Xavier Gómez-Batiste, MD, Federico Madrid, MD, Francisco Moreno,Albert Gracia, MD, Jordi Trelis, MD, Maria Nabal, MD, Ramón Alcalde, MD,Josep Planas, MD, and Helena Camell, MD.

Servei de Cures Palliatives, Institut Català d’Oncologia (X.G.-B., F.Ma., F.Mo., J.T.) L’Hospitalet, Barcelona; Medical Department (A.G.) Grupo Ferrer, Barcelona; Hospital Universitario “Arnau de Vilanova” (M.N.), Lleida; Hospital de Santa Caterina (R.A.), Girona; Hospital de l’Esperana (J.P.), Barcelona; and Hospital Residència Sant Camil (H.C.), Barcelona, Spain

Abstract

Breakthrough pain (BTP), a transitory exacerbation of pain superimposed on a background of persistent, usually adequately controlled pain, has been reported to occur in 50% to 75% of cancer patients. However, a 23% prevalence of BTP was recently reported in a study of Spanish patients with advanced cancers, showing probably a low detection rate of this clinical problem. The purpose of the present study was to determine the prevalence of BTP among oncology patients managed by palliative care teams in Catalonia, Spain, and to characterize the frequency, intensity, and treatment of BTP episodes. Sixty-two teams studied 397 patients on a predetermined index day. BTP was reported by 163 (41%) patients, with a total of 244 episodes (mean 1.5 episodes/patient/day). Mean (SD) intensity of BTP episodes was 7.3 (2.0), compared with 2.9 (2.7) for persistent pain (both 0–10 scales). Morphine was used to treat 52% of BTP episodes, while 25% were untreated. These findings indicate that BTP remains underrecognized and undertreated in Spain.

J Pain Symptom Manage 2002;24:45–52.

© U.S. Cancer Pain Relief Committee, 2002.

Key Words

Breakthrough pain, incident pain, pain, cancer, oncology, palliative care

46 Gómez-Batiste et al. Vol. 24 No. 1 July 2002

day.

2

Due to the fact that BTP can negatively af-fect psychological and functional outcomes,

5

the knowledge of how to successfully manageBTP can significantly affect the quality of life ofpatients.

The pathophysiology of BTP can be somatic,visceral, or neuropathic, and most often can betied to the same mechanism that causes thepersistent pain.

6,7

By definition, BTP is eitherof rapid/paroxysmal onset, with a peak of in-tensity before 3 minutes, or it can developmore gradually, reaching peak intensity be-tween 3 and 30 minutes.

2

Like persistent can-cer pain, BTP can be directly related to the lo-cation of the neoplasia, the effects of thetreatment, or other etiologies.

BTP can be classified according to precipi-tating events. BTP related to movement is gen-erally called “incident pain.” Incident pain canbe caused by voluntary movements such aswalking or sitting down, or be caused by invol-untary movements such as intestinal or ure-thral distention. BTP that is not tied to the reg-ular analgesic schedule or to movements orbody functions is called “spontaneous or idio-pathic breakthrough pain.” The exacerbationsof pain that typically occur at the end of thedosage interval of persistent chronic opioids(“around the clock” medication) are called“end of dose failure.”

Recent studies have estimated the preva-lence of BTP. In a survey of 90 patients at Me-morial Sloan-Kettering Cancer Center, 64% ofpatients reported experiencing BTP.

2

Onestudy in Germany sought to determine thenumber of patients with cancer who experi-enced “transient pain,” defined as any eventcharacterized by pain intensity above their per-sistent chronic pain and transient in nature. Inthis study of 613 patients, 39% were found tohave transient pain.

8

In a U.S. survey of 22 hos-pice patients, 86% experienced breakthroughcancer pain.

9

In a previous study of the prevalence of theuse of opioids in Spain, the reported preva-lence of BTP was 23%.

10

Because this preva-lence was lower than the majority of publishedstudies, we suspected a relative underdetectionand a consequent undertreatment of BTP inour area. The objective of this study was to de-termine the prevalence of BTP among oncol-ogy patients managed by the palliative careteams of Catalonia, Spain. In addition, we

sought to characterize the BTP episodes basedon etiology, pathology, temporal characteristics,and effectiveness of therapeutic treatment.

Methods

This was an observational and cross-sectionalstudy designed to measure the prevalence ofcancer-related BTP. The study populationcomprised oncology patients that were seen ona predetermined index day. Patients were in-terviewed regarding their persistent pain andthe frequency, characteristics, and treatmentof their BTP. This study was approved by theEthics Committee of the Vall de Hebron Hos-pital (Autonomous University of Barcelona).

Patient Selection and Procedures

All of the palliative care teams in Cataloniawere offered participation in this study (

n

�

103 teams). Most patients who were seen onthe measurement day were eligible for thestudy. Patients who were not eligible for partic-ipation included those being seen for the firsttime on the study day or the previous day,those who had cognitive impairment , or thosewho had a life expectancy of less than a week.

On the study day, the team interviewed allpatients who were eligible for the study,whether patients had a scheduled or unsched-uled appointment. Assessments could havetaken place in palliative care units, the hospi-tal, in outpatient offices, or at the patient’shome. In addition to performing routine ap-pointment procedures, the team recordedstudy information in a data collection note-book. The data recorded the BTP episodes inthe last 24 hours.

Data Collection

Due to the diversity of painful experiencesamong oncology patients, a broad definition ofBTP was selected. For the purposes of thisstudy, cancer-related

breakthrough pain

was de-fined as transitory increase of pain of higherthan moderate intensity, that occurred sud-denly over a relatively well-controlled chronicpain level, which was, at least, moderate in in-tensity.

2

Persistent chronic pain data collected in-cluded basic pathology of the primary neo-plasm (location of the primary tumor and theextent of the illness) and intensity of the persis-

Vol. 24 No. 1 July 2002 Survey of Breakthrough Cancer Pain in Spain 47

tent chronic pain. Current treatment used forpersistent chronic pain was recorded accord-ing to the therapeutic levels of WHO (Level 1

�

non-opioid analgesic with or without adjuvantmedication, Level 2

�

weak opioid with orwithout adjuvant medication, Level 3

�

potentopioid with or without adjuvant medication).

1

Included in the definition of potent opioidswere morphine, fentanyl, and methadone. In-cluded in the definition of weak opioids werecodeine, tramadol, and propoxyfene.

BTP was characterized according to its tem-poral characteristics (number of episodes/day,speed of onset, and duration); severity (using averbal numeric scale that ranged from 0

�

ab-sence of pain, 2

�

light pain, 5

�

moderatepain, 7

�

intense pain through 10

�

worstpain imaginable); and type (spontaneous, inci-dent, or end-of-dose failure). BTP treatmentand effectiveness of treatment were evaluated.Data on the time required to achieve signifi-cant relief of BTP were also collected.

Data Analysis

Descriptive parameters were used to charac-terize the study sample and characteristics ofthe BTP episodes. Statistical tests were per-formed using SPSS, version 9. The prevalenceof BTP, along with a 95% confidence interval(CI 95%), was calculated as the percentage ofpatients who experienced at least one episodeof BTP on the index day. The incidence ofBTP episodes was described as the number ofepisodes of BTP experienced per patient onthe index day. An analysis of variance (ANOVA)was performed to ascertain if the relationshipbetween the intensity of the BTP episode wassignificantly related to the type of pain of theBTP episode (spontaneous, incident, or end-of-dose failure). Nonparametric tests were usedto evaluate significant differences in the valuesof certain BTP and chronic persistent pain vari-ables when patients were subdivided accordingto BTP or chronic persistent pain variables.These tests included Mann–Whitney U, Kruskall–Wallis, and chi-square tests. Significance was setat level of 0.05, two-tailed.

Results

Participation in the study was offered to the103 palliative care teams of Catalonia, of which73 accepted. Of these, 11 were excluded for

poor sample selection, and the remaining 62were included in the analysis. Of the 407 po-tential subjects, 397 evaluable patients were in-cluded in the study. Five patients were ex-cluded from the study because they were notoncology patients and 5 patients were ex-cluded due to cognitive deterioration whowere not excluded previously in the first selec-tion. In 92% of the cases, the patients wereseen for a regularly scheduled appointment. In4% of the cases, the patients were seen for un-scheduled visits, and data were not availablefor the remaining 4% of patients. The mostcommon place where the interview took placewas the hospital (49%), followed by patients’homes (28%).

Patient Characteristics

Approximately half of the 397 patients weremen (Table 1). Patients’ ages ranged from 7 to92 years, and the mean (SD) age was 68.3(14.1) years. The most frequent location of the

Table 1

Patient Characteristics (

n

�

397)

Sex (

n

, %)Female 184 (47)Male 200 (50)Missing data 13 (3)

Age (years)Mean (SD) 68.3 (14.1)Median 71Range 7–92

Location of primary tumor (

n

, %)Colorectal 60 (15)Lung 58 (15)Breast 41 (10)Head and neck 30 (8)Prostate 29 (7)Gastric 22 (6)Pancreas 18 (4)Carcinoma of unknown origin 18 (4)CNS 15 (4)Bladder 14 (4)Multiple myeloma 10 (2)Kidney 10 (2)Lymphoma 9 (2)Endometrial 8 (2)Liver 7 (2)Other 48 (12)

Spread of Illness (

n

, %)Local 93 (23)Regional 112 (28)Metastatic 226 (57)

Type of Metastatic Spread (

n

, %)Bone 110 (49)Lung 53 (26)Liver 71 (31)Other 74 (32)

48 Gómez-Batiste et al. Vol. 24 No. 1 July 2002

primary tumor was colorectal (15%), lung(15%), and breast (10%). The majority of pa-tients (56.9%) had metastatic cancer, with themost frequent site of metastases being thebone (49%). Approximately one-third of pa-tients who reported metastases (31%) had met-astatic spread to the liver.

Persistent Chronic Pain Characteristics

The mean (SD) value for persistent chronicpain intensity was 2.9 (2.7), with a medianvalue of 2 and a range from 0 to 10. About 33%of patients rated the intensity as 0 or 1, 35% ofpatients rated the intensity between 2 and 4,and 25% of patients rated the intensity as 5 orgreater (data were not available for 7% of pa-tients). The majority of patients (54%) used apotent opioid with or without adjuvant medica-tions to manage their persistent chronic pain.About 17% of patients used a weak opioid withor without adjuvant medications for their per-sistent chronic pain, and 16% used a non-opi-oid analgesic with or without adjuvant medica-tion (data were not available for 13% of patients).The most commonly used opioid for persistentchronic pain was morphine (81%), followed bytransdermal fentanyl (15%), and methadone(5%). Of the patients using morphine, 56%used oral morphine, 32% used subcutaneousmorphine, and 8% used other routes such asintravenous, epidural, or intrathecal (data werenot available for 5% of patients). The mostcommon adjuvant medications used by patientsincluded corticosteroids (43%), nonsteroidalantiinflamatory drugs (NSAIDs; 33%), antide-pressants (16%), and anticonvulsants (12%).

Patients with regional spread of their illness(regional node involvement) had significantly(

P

�

0.05) lower mean (SD) persistent chronicpain intensity scores than patients with eitherlocal (primary tumor) spread of illness or met-astatic (distant methastases) spread of illness,2.51 (2.6) vs. 3.09 (2.6), respectively (

P

�

0.042). Patients who were interviewed in theirhomes reported significantly higher persistentchronic pain intensity scores than patients whowere interviewed by a hospital support team,mean (SD) on a 0–10 scale, 3.5 (3.0) vs. 1.5(1.9), respectively (

P

�

0.002). Patients who re-ported experiencing BTP reported a signifi-cantly higher mean (SD) persistent chronicpain intensity score than patients without BTP,3.9 (2.7) vs. 2.1 (2.4), respectively (

P

�

0.0001).

Breakthrough Pain Characteristics

Approximately 41% (95% CI: 33.5%, 48.7%)of patients (163/397) reported experiencingat least one episode of BTP on the index day(Table 2). There were no statistically signifi-cant relationships between the location wherethe interview took place and the percentage ofpatients who experienced BTP.

A total of 244 episodes of BTP were reportedby the 163 patients experiencing BTP on theindex day, for an average of 1.5 episodes perpatient per day. Of the 244 BTP episodes, 60%were of rapid onset (as described by the pa-tient) and 39% were of gradual onset. Themean (SD) duration of the BTP episodes was33.8 (32.0) minutes, and the mean (SD) inten-sity of the BTP episodes was 7.3 (2.0). Slightlyover half of the BTP episodes were incidentpain (52%), and the most frequent trigger wasmobilization (74% of incident pain episodes).The next most common triggers of incidentpain, although considerably less frequent thanmobilization, were ingestion (5%), defecation(4%), and coughing (3%).

Table 2

Description of Breakthrough Pain Episodes

Distribution of BTP Episodes Patients Reported (

n

, %)0 234 (59)1 110 (28)2 33 (8)3 15 (4)4 2 (0.5)5 3 (1)

Onset of BTP episodes (

n

, %)Gradual 96 (39)Rapid/paroxysmal 145 (60)Not specified 3 (1)

Duration of BTP episodes, mean (SD) (minutes) 33.8 (32)

�

15 minutes 31

�

15 to

�

30 minutes 33

�

30 to

�

60 minutes 23

�

60 to

�

120 minutes 5

�

120 minutes 2Not specified 6

Intensity of BTP episodes (0 to 10 scale)Mean (SD) 7.3 (2.0)Median 8Range 2–10

Type of BTP (No., %)Incident 128 (52)Spontaneous 78 (32)End of dose failure of persistent chronic

opioid 37 (15)Not specified 1 (0.4)

BTP

�

breakthrough pain.

Vol. 24 No. 1 July 2002 Survey of Breakthrough Cancer Pain in Spain 49

The characteristics of BTP were evaluatedaccording to the type of BTP, that is, spontane-ous, incident, or end-of-dose failure (Table 3).The type of BTP significantly influenced theonset of BTP, with approximately 76% of inci-dent BTP episodes being unexpected or parox-ysmal in onset, compared with 52% of sponta-neous breakthrough pain episodes and 24% ofend-of-dose episodes (

P

�

0.0001). The type ofBTP was significantly related to the duration ofBTP episodes. BTP episodes of the incidenttype were significantly shorter than BTP epi-sodes of the spontaneous or end-of-dose failuretypes, 26.7 minutes vs. 43.9 and 36.4 minutes,respectively (

P

�

0.0001). The type of BTP wasalso significantly related to the proportion ofpatients treating the BTP episode. BTP epi-sodes of the spontaneous and end-of-dose fail-ure types were treated by 91% and 92% ofpatients, respectively, compared with 61% ofpatients with BTP episodes of the incident type(

P

�

0.0001).The analgesics used to treat BTP episodes

appear in Table 4 according to the type ofBTP, although there were no significant differ-ences in treatment frequency by type of BTP.For all types of BTP, morphine was used totreat 52% of the BTP episodes, mostly givensubcutaneously or orally. Other common treat-ments used for BTP episodes included NSAIDs(7%), tramadol (4%), benzodiazepines (4%),

and paracetamol (4%). Approximately 25%(60/243) of the BTP episodes were untreated.

The relationship between different treat-ments (or nontreatment) of BTP to intensity ofBTP episodes, time to significant pain relief,and duration of BTP episodes was evaluated(Table 5). The mean (SD) pain intensity wassignificantly greater for 177 treated than for 60untreated of BTP episodes, 7.6 (1.8) vs. 6.5(2.2), respectively (

P

�

0.001). The mean (SD)time to significant pain relief was significantlyhigher for treated than for untreated BTP epi-sodes, 24.9 (16.3) vs. 12.6 (14.9) minutes, re-spectively (

P

�

0.0001). It should be noted,however, that of the 60 untreated episodes, 35(58%) did not indicate a time until pain relief,indicating that patients may not have attainedadequate relief, while of the 183 episodes thatwere treated, only 2 (1%) did not indicate atime until pain relief. The mean (SD) durationof BTP episodes was also significantly longerfor treated episodes compared with untreatedepisodes, 38.8 (33.9) vs. 18.2 (17.4) minutes,respectively (

P

�

0.0001).For treated BTP episodes, the mean time to

significant pain relief appeared to be shortestfor episodes treated with morphine plus an-other medication (excluding NSAIDs), althoughthe number of episodes in this group was small(see Table 5). BTP episodes treated with subcu-taneous morphine were associated with a signifi-

Table 3

Characteristics of Breakthrough Pain by Type of Breakthrough Pain

Type of Breakthrough Pain

Variable Spontaneous Incident End-of-Dose

P

Number of BTP Episodes by Type of BTP 78 128 37Onset of BTP (

n

, %)Unexpected or paroxysmal 40 (52) 96 (76) 9 (24)

�

0.0001

a

Gradual 37 (48) 31 (24) 28 (76)Duration of BTP (minutes)

Mean (SD) 43.9 (42.8) 26.7 (25.5) 36.4 (16.1)

�

0.0001

b

Median 30 20 30Range (2–180) (1–120) (5–60)

BTP Episodes (

n

, %)Without treatment 7 (9%) 50 (39%) 3 (8%)

�

0.0001

c

With treatment 71 (91%) 78 (61%) 34 (92%)

BTP

�

breakthrough pain.

a

Percentage of patients with unexpected/paroxysmal onset of BTP was significantly higher in patients with incident BTP. Percentage of patientswith gradual onset of BTP was significantly higher in patients with BTP due to end-of-dose failure of the around-the-clock medication (chi-square,

P

�

0.0001).

b

Relationship between duration of episode and type of breakthrough pain was statistically significant (Kruskall–Wallis test,

P

�

0.0001), with inci-dent type presenting shorter duration of episodes than other two types. The differences between the spontaneous pain and end-of-dose pain werenot statistically significant.

c

Percentage of patients without any treatment significantly higher for group of incident pain than for the other two types of pain (chi-square,

P

�

0.0001).

50 Gómez-Batiste et al. Vol. 24 No. 1 July 2002

cantly shorter mean (SD) time to significantpain relief than episodes treated with oral mor-phine, 17.0 (11.2) vs. 32.8 (17.9) minutes, re-spectively (

P

�

0.0001). The mean (SD) dura-tion of BTP episodes also appeared to beshortest with morphine plus another medica-tion, 23 (9.8) minutes (

n

�

10). Episodes thatwere treated with morphine alone had a mean(SD) duration of 37.1 (25.2) minutes (

n

�

108).

Discussion

The prevalence of BTP in our study, calcu-lated as the percentage of patients who experi-enced BTP on the index day, was 41% (95% CI;33.5%, 48.7%). This finding is higher than the23% prevalence reported in our previous study

10

and is more consistent with other published re-search.

2,8

Of the 163 patients in our study whoreported experiencing BTP, the majority (67%)experienced one episode of BTP on the indexday. The mean (SD) duration of BTP episodeswas 33.8 (32.0) minutes and the mean (SD) in-tensity was 7.3 (2.0) on a 0 to10 scale. The typeof BTP episodes was mostly commonly of inci-dent pain (52.5%) and the most utilized treat-ment for the episodes of pain was morphine(52%). The mean (SD) time until significant al-leviation of the pain was 23.4 (16.6) minutes.

Patients with the highest persistent chronicpain intensity were more likely to experiencean episode of BTP. The patients interviewedduring house-call visits reported poorer con-trol of their persistent chronic pain than pa-

tients interviewed in hospital visits, the inter-view location was not associated significantlywith the probability of experiencing BTP.

BTP episodes of the incident type were lessfrequently treated than those of the spontane-ous or end-of-dose failure types. They were alsoof shorter duration than the other types of BTP.This may be due to the fact that the patient rec-ognizes this type of pain and knows it will prob-ably resolve. For incident pain that the patientknows will be of short duration or of bearableintensity, the patient may choose not to treatthe episode. This hypothesis is supported by thefinding that untreated episodes were associatedwith shorter time until pain relief, shorter dura-tion of the episode, and lower pain intensity.

Although the percentage of patients withcancer-related BTP in this study sample is moreconsistent than our previous study with per-centages described by other studies in usingother methods, the number of BTP episodesper patient per day appears to be underesti-mated. The finding that two-thirds of patientswith BTP reported only 1 episode on the indexday stands in contrast with the reports of otherresearchers that patients typically experiencebetween 1 and 4 episodes of BTP each day.

2,11

We can only speculate that this disparity maybe due to the survey instrument used, where in-vestigators interviewed the patients at a singlepoint in time and sometimes used retrospectiveinformation, or cultural differences wherebypatients may have had a tendency to underre-port their BTP and describe only one of their

Table 4

Description of Treatments Used for Breakthrough Pain Episodes

Type of Breakthrough Pain

Variable Spontaneous Incident End-of-Dose

Number of BTP episodes by type of BTP 78 128 37Treatment Used (

n

, %)No treatment 7 (9) 50 (30) 3 (8)Morphine alone 39 (50) 49 (38) 26 (70)Morphine with NSAIDs or others 7 (9) 6 (5) 0 (0)NSAIDs alone 4 (5) 3 (2) 3 (8)NSAIDs with others 3 (4) 0 (0) 0 (0)Methadone 0 (0) 3 (2) 0 (0)Others

a

18 (23) 15 (12) 5 (14)Unknown 0 (0) 2 (2) 0 (0)

Route of Morphine Administration (

n

, %)Oral 14 (18) 27 (21) 11 (30)Subcutaneous 30 (38) 24 (19) 10 (27)Unknown 2 (3) 3 (2) 5 (14)

BTP

�

Breakthrough pain; NSAIDs

�

nonsteroidal anti-inflammatory drugs.

a

The “other” category included acetaminophen (paracetamol), tramadol, benzodiazepine, and metamizole.

Vol. 24 No. 1 July 2002 Survey of Breakthrough Cancer Pain in Spain 51

BTP episodes if the rest of the episodes that dayhad the same characteristics. Other possible ex-planations of differences in results between thissurvey and other studies include using multipleteams and interview locations, patients’ diseasecharacteristics, intensity and treatment of thepersistent chronic pain, and treatment optionsavailable for BTP, although we have no data tosupport any of these potential factors.

Nevertheless, this survey provides importantnew information regarding the prevalence andcharacteristics of BTP in Spain. Our results sug-gest that our cancer patients may not identifyepisodes of BTP as often as patients in other set-tings and countries. Thus, better informingSpanish cancer patients and their physiciansabout the recognition and characteristics ofBTP, and the treatment options available forBTP, could serve to improve the overall manage-ment of cancer pain and patients’ quality of life.

Acknowledgments

The authors gratefully acknowledge the ef-forts of all other collaborators who contributedtheir efforts to this study. These collaboratorsare: Dr. D. Pascual, CAP Alt Penedés—PADES;Dr. N . Castells, CAP de Balàfia; Dr. Balello, CAPII (Sta. Coloma de Gramanet); Dr. J. Cor-nudella, Casal de Curació; Dr. C. Charlez, Cen-

tre Socio-Sanitari Ciutat de Reus; Dr. C. Ortega,Centre Socio-Sanitari de Manresa; Dr. J. Cunill,Centre Socio-Sanitari El Carme; Dr Vallvé,Clínica Barceloneta; Dr. I. Grimau, ConsorciHospitalari del Parc Taulí-UCP; Dr. G. Canta-rell, Corporació Sanitària Parc Taulí; Dr. S. Gal-lardo, PADES Parc Taulí, Dr. F. Gili, Creu RojaHospitalet; Clínica del Dolor Creu Roja Hospi-talet; Dr. A. M. Gort, CSS—Arnau de Vilanova;Dr. L. Nadal, CSS—Creu Roja ; Dr. F. Capdevila,Fundació Sanitària d’Igualada; Dr. D. Carrión,Hospital Comarcal Mora d’Ebre—UCP; Dr I.Coca, Hospital de Figueres; Dr. J. Planas, Hospi-tal de l’Eespârança; Dr. J. Girbau, Hospital del’Esperit Sant—UFISS; Dr. V. Santacruz, Hospi-tal de la Santa Creu (Tortosa); Dr. J. Porta, Hos-pital de la Sta. Creu; (Vic); Dr. J. Sota, HospitalEvangèlic; Dr. G. Morlans, Hospital Gral. deGranollers—UCP; Dr. J. Canals, Hospital Jaumed’Urgell; Dr. H. Camell, Hospital ResidènicaSant Camil; Dr. F. Lynd, Hospital Sant Gervasil;Dr. N. Cortada, Hospital Sant Jaume de Calella—PADES—UFISS; Dr. D. Rodríguez, HospitalSant Joan de Déu de Reus—UFISS; Dr. Gascón,Dr. Gabriel de Febrer, Hospital Sant Joan deDéu de Reus ; Dr. C. Sala, Hospital SantLlàtzer—UCP; Dr. R. Alcalde, Hospital SantaCaterina; Dr. M. Nabal, Hospital Univ. Arnau deVilanova—UFISS; Dr. A. Padrol, Hospital Uni-versitari Joan XXIII—UFISS; Dr. Estíbalez, Hos-

Table 5

Characteristics of Breakthrough Pain Episodes by Treatment for Breakthrough Pain Episode

Intensity of BreakthroughPain Episode (0 to 10 scale)

Mean (SD)

Time to Significant Pain Relief (minutes)

Mean (SD)

Duration of BreakthroughPain Episode (minutes)

Mean (SD)

Not Treated (n � 60, 25, 55)a 6.5 (2.2) 12.6 (14.9)b 18.2 (17.4)Treated (n � 177, 181, 174) 7.6 (1.8) 24.9 (16.3) 38.8 (33.9)

P � 0.001c P � 0.0001c P � 0.0001c

Treatment used for BTP episodeMorphine (n � 111, 114, 108) 7.7 (1.7) 224.9 (16.0) 37.1 (25.2)Morphine with NSAIDs (n � 4) 9.5 (1.0) 35.0 (17.3) 43.8 (30.9)Morphine with othersd (n � 9, 10, 10) 9.4 (0.9) 12.5 (7.6) 23.0 (9.8)NSAIDs (n � 10, 9, 9) 7.7 (2.4) 26.2 (19.8) 58.4 (70.5)NSAIDs with othersd (n � 3) 8.0 30.0 180.0Methadone (n � 2, 3, 3) 5.5 30.0 26.7Othersd (n � 36, 38, 35 6.4 (1.6) 26.1 (18.3) 32.1 (22.2)

Route of Morphine AdministrationOral (n � 51, 52, 51) 7.8 � 1.7 32.8 � 17.9 41.4 � 26.1Subcutaneous (n � 60, 64, 60) 7.6 � 1.7 17.0 � 11.2 32.5 � 21.7

NSc P � 0.0001c P � 0.043c

aWhere the sample size varies across variables, n of BTP episodes is presented for each column, respectively. Standard deviations (SD) are not pre-sented for n � 4.bMean time to spontaneous pain relief.cMann–Whitney U test.dThe “other” category included acetaminophen (paracetamol), tramadol, benzodiazepine, and metamizole.BTP � breakthrough pain; NSAIDs � nonsteroidal anti-inflammatory drugs.

52 Gómez-Batiste et al. Vol. 24 No. 1 July 2002

pital Vall d’Hebrón—UFISS; Dr. J. Trelis, Insti-tut Català d’Oncología—C. Externes; Dr. F.Moreno, Institut Català d’Oncología—UCP; Dr.F. Madrid, Institut Català d’Oncología—UFISS;Dr. J. Pizaca, PADES—CAP Maresme; Dr. C.Bassedas, PADES—Garbí; Dr. P. Castañera,PADES—El Prat; Dr. N. Calvo, PADES Gràcia;Dr. Galdina Valls, PADES Dreta Eixample—MUTUAM; Dr. M. Bleda, PADES Esquerra Eix-ample; Dr. M.D. Torremorell, PADES HospitalSant Llàtzer; Dr. M. Liras, PADES L’Hospitalet;Dr. M. Espier, PADES Les Corts; Dr. X. Busquet,PADES Manresa; Dr. Quera, PADES ManreseSud; Dr. M. Noriana, PADES Mollet; Dr. Canel-las, PADES Nou Barris; Dr. JMP Castejó, PADESOsona; Dr. R. González, PADES Pla d’Urgell—Segrià—Garrigues; Dr. R. Casañas, PADES SantAndreu; Dr. M. Calafell, PADES Sant Feliu;PADES Sant Martí; Dr. M. Amor, PADES Sants;Dr. N. Arrarás, PADES Segarra—Urgell—Nogu-era; Dr. E. Justo, PADES Vilanova; Dr. M.Doménech, Dr. Mercè Clols, Dr. Jose Fuentes,PIUS Hospital de Valls; Dr. I. Contel, PoliclínicaComarcal del Vendrell; Dr. P. Loncan, UCP—Clínica Santa Susanna; Dr. M. Capo, Hospital deSant Llàtzer—UFISS; Dr. G. Corbera, PADESMútua Terrassa; Dr. M. Esteban, PADES Reus;Dr. Seguera, Dr. Fontanet, Clínica del DolorJoan XXIII; Dr. Castejón, Hospital de SantaCreu (Vic); PADES Sarrià Sant Gervasi; and Dr.C. Espinosa, Residencia Cabanelles.

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