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Original Article |

Colonic Propulsive Impairment in Intractable Slow-Transit Constipation FREE

Gabrio Bassotti, MD; Fabio Chistolini, MD; Francis Sietchiping Nzepa, MD; Antonio Morelli, MD
[+] Author Affiliations

From the Gastroenterolgy and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia Medical School, Perugia, Italy.


Arch Surg. 2003;138(12):1302-1304. doi:10.1001/archsurg.138.12.1302.
Text Size: A A A
Published online

Hypothesis  Intractable constipation, especially of the slow-transit subtype, may represent several pathophysiologic entities with a common final symptomatic appearance. An overall impairment of colonic propulsive activity may represent a major disease mechanism.

Design  Case series.

Setting  Tertiary university hospital.

Subjects  Twenty-nine severely constipated patients with clinical and homogeneous features of slow-transit constipation that were unresponsive to conventional medical measures and 16 age-matched healthy volunteers.

Interventions  Twenty-four–hour manometric recordings obtained in patients and controls to assess high- and low-amplitude colonic propulsive activity.

Results  Compared with controls, patients showed heavily reduced high-amplitude propagated activity (average, <1 event per subject per day). No differences were found in low-amplitude propagated activity.

Conclusions  Patients with severe constipation that is refractory to medical treatment may display an important reduction of colonic forceful propulsive activity. This may justify a surgical approach, which may offer the best results in such patients. It is, however, important to obtain thorough physiologic documentation before such a drastic approach is considered. The residual low-amplitude propulsive activity might represent a partially compensatory mechanism in these patients. Studies in more homogeneous groups of such patients are needed.

FUNCTIONAL constipation encompasses a group of functional disorders that exhibit persistent difficult, infrequent, or seemingly incomplete defecation and infrequent, lumpy, or hard stools.1 This symptom is very common and may occur in up to 20% of populations, depending on demographic factors, sampling, and the definitions employed.2 The term constipation is probably better viewed as a sort of semantic umbrella, covering pathophysiologic subtypes, among which 2 major groups may now be identified: slow-transit constipation (STC) and pelvic floor dysfunction. A third group includes patients with both STC and pelvic floor dysfunction.3

Slow-transit constipation is thought to have, as a primary defect, slower than normal movement of contents from the cecum to the rectum.4,5 However, it is likely that the term STC encompasses a range of disorders with a definite common abnormality—prolonged colonic transit time6—as shown by the heterogeneity of the clinical signs and symptoms.79 Although a few studies have shown that severely constipated patients may have altered anorectal1012 and colonic1315 motor function, no data exist on colonic propulsive function in homogeneous and consistent groups of such patients.

The purpose of our study was to assess colonic propulsive activity in a relatively large group of STC patients with homogeneous characteristics and a particularly severe clinical picture. Our working hypothesis was that such activity was particularly impaired in these patients.

PATIENTS

Twenty-nine severely constipated women (age range, 37-52 years) entered the study. The patients' characteristics not only fulfilled the Rome II criteria for functional constipation16 but they exceeded the criteria in symptom duration and severity. The study inclusion criteria were (1) long-standing (>3 years) history of constipation; (2) fewer than 1 evacuation per week; (3) absence of frequent (>2 episodes per month) or chronic abdominal pain; (4) sensation of incomplete evacuation in more than one quarter of defecations; (5) negative history for (sub)occlusive episodes; (6) no history of major abdominal or pelvic surgery; and (7) unresponsiveness to appropriate medical treatment. All patients retained more than 20% of 40 ingested radiopaque markers within the colon after 96 hours, which is the mean + 2 SDs for healthy controls studied in our laboratory.17 Causes of secondary constipation were excluded by drug history (special care was taken in excluding the use of antidepressants18,19), physical examination, and laboratory screening (blood chemical analysis, thyroid hormones, and, where appropriate, oral glucose tolerance test, sex hormone profiles, and antinuclear antibodies). To exclude organic diseases or mechanical causes of constipation and megacolon or megarectum, each patient underwent double-contrast barium enema, colonoscopy, and abdominal ultrasound scans. The absence of Hirschsprung disease was demonstrated by normal relaxation of the internal anal sphincter on anorectal manometry.20 No patient had evidence of pelvic floor dyssynergia, as documented by anorectal manometry and defecography.

CONTROLS

Sixteen healthy volunteers (8 men, 8 women; age range, 35-48 years) were recruited as a control group, matched for age but not for sex. However, there is evidence that gender does not influence colonic propulsive activity.21,22 No volunteer complained of abdominal pain, abdominal distention, or disturbances in bowel habits. The average defecation frequency was 1 per day. A careful drug history was obtained for each subject to ascertain that none had taken drugs known to influence gastrointestinal motility during the 2 weeks before the study. No volunteer had previously undergone abdominal or pelvic surgery.

PROCEDURE

Twenty-four–hour colonic motor activity in patients and controls was studied by a previously described manometric technique.2325 After an overnight fast, an 8-lumen manometric probe with side holes spaced 12 cm apart (outer diameter, 4.5 mm; inner diameter for each lumen, 0.8 mm) was introduced into the colon by a colonoscope. Bowel cleansing was achieved with a semiliquid diet for 2 days and magnesium sulfate (30 g by mouth 36 hours before colonoscopy) and tap water enemas (12 and 6 hours before the procedure). The probe was positioned by advancing it together with the endoscope, with the tip of the probe fixed to the tip of the colonoscope by a silk thread held by biopsy forceps inside the operative channel of the endoscope. Intravenous diazepam (5 mg) was used for sedation. Once the desired portion of the viscus was reached (at least the proximal part of the transverse colon), the forceps were opened and the colonoscope gently withdrawn, aspirating air as completely as possible. The probe was then connected to external physiologic pressure transducers and to a low-compliance pneumohydraulic system, perfusing bubble-free distilled water at a constant rate of 0.2 mL/min. At this perfusion rate, distal occlusion of individual recording ports yields a rise rate of more than 100 mm Hg/s. Intraluminal pressures were recorded by a multichannel paper recorder coupled to the transducers (paper speed, 0.5 mm/s).

After the probe was positioned, a radiologic control was made to assess catheter placement. Then the patients were moved to the motility laboratory, where they rested for 2 to 4 hours to allow elimination of the air from the colon and recovery from the endoscopy procedure. Thereafter, a 24-hour recording was obtained. During the recording, 2 1000-kcal mixed meals and a 450-kcal breakfast were served, as previously described.26 At the end of the recording session, a fluoroscopic check was obtained to ascertain that no major (>10 cm) displacement of the probe had occurred.

After careful explanations about the aims of the study, both patients and controls gave informed consent. The studies were carried out in accordance with local ethical guidelines, following the recommendations of the Declaration of Helsinki.

DATA ANALYSIS

All data were calculated manually by one of us (G.B.). High-amplitude propagated contractions (HAPCs) were defined as pressure waves that (1) were observed at 3 ports sequentially with a delay of 1 to 10 seconds between peaks seen at adjacent sites and (2) had amplitudes of at least 75 mm Hg of absolute pressure or a 50-mm Hg increase from the baseline at all 3 sites.27 Low-amplitude propagated contractions (LAPCs) were defined as for HAPCs but with amplitudes of less than 50 mm Hg of absolute pressure at all 3 sites.28 The following HAPC and LAPC variables were taken into consideration for both groups: (1) the total number per 24 hours; (2) their mean amplitude (in millimeters of mercury), by subtracting mean resting colon pressure from the peak of pressure waves; and (3) their correlation with abdominal sensations, pain, or flatus. To be correlated, a propulsive event of either amplitude would have to occur within 10 minutes from the event, signaled on the tracing by an event marker operated by the patient, who could not view the tracing itself.

STATISTICAL ANALYSIS

The t test was used for unpaired data. Data are expressed as mean ± SEM. P<.05 indicates rejection of the null hypothesis.

The probe was positioned near the hepatic flexure in 25 patients and 12 controls; in the remaining subjects, it was positioned between the mid and the distal transverse colon. The fluoroscopic check at the end of each recording showed that no major displacement of the catheter had occurred. Each subject was able to complete the study without discomfort.

In STC patients, the average number per subject per day of HAPCs was decreased to a significant and important extent with respect to controls (0.62 ± 0.2 vs 5.5 ± 0.78; P<.001), whereas no differences were found in HAPC amplitude (106.3 ± 8 vs 109.5 ± 7 mm Hg; P = .98) and LAPC variables (average number per subject per day, 50.9 ± 10 vs 46.3 ± 8; P = .96; average amplitude, 19.4 ± 1.8 vs 22.5 ± 2.4 mm Hg; P = .87) (Table 1).

Table Graphic Jump LocationHAPC and LAPC Variable in Patients With Slow-Transit Constipation and Controls*

Concerning relationships with abdominal sensations, HAPCs were associated with a defecatory stimulus in 4 controls (25%); no patients reported such sensation. Low-amplitude propagated contractions were associated with the passage of flatus on at least 1 occasion in 4 controls (25%) and in 2 patients (7%), and with mild defecatory stimulus in 9 patients (31%) on at least 1 occasion, especially following meals.

The pathophysiologic mechanisms of STC are still widely debated.29 This study demonstrates that in severe constipation that is refractory to conventional medical treatment, the forceful colonic propulsive activity equivalent to mass movements, ie, the HAPC, is so impaired that it is detectable, on average, on less than 1 occasion per day. This is a notable finding, especially because it was consistently present in a relatively large group of patients with homogeneous characteristics. Although there was minimal propagated activity, as evidenced by the preservation of LAPCs (which may exert some propulsive activity in humans30), this activity was not entirely able to compensate for the lack of HAPCs (as happens in less severe forms of STC through an increase of such an activity [G.B., unpublished data, 2003]), since their number showed no increment with respect to controls. It is conceivable that in a more advanced stage, the loss of LAPCs might lead to a true colonic inertia, in which no propulsive activity is recorded.

In constipated patients who are unresponsive to medical measures, a history of surgery is often indicated.31 When a thorough physiologic assessment reveals convincing evidence of STC and no evidence of outlet obstruction, total colectomy with ileorectal anastomosis may offer sustained relief of constipation.32,33 It remains to be established whether an adjunct assessment by means of colonic manometry may offer further evidence to support a surgical approach, for instance, through a demonstration of ineffective propulsive colonic capability. Our institution now uses such an approach for selected cases.34 However, this technique is not yet readily available, is somewhat invasive, and is not easy to apply in the routine practice of surgery. This technique, therefore, might be best used in cases where STC is suspected but cannot be proven by the conventional methods. Careful physiologic evaluation is strongly advisable for patients with STC that has been unresponsive to conventional therapy. We recommend this to obtain the best results and, possibly, suggest a more targeted therapeutic approach.

Corresponding author and reprints: Gabrio Bassotti, MD, PhD, Strada del Cimitero, 2/a, 06131 San Marco (Perugia), Italy (e-mail: gabassot@tin.it).

Accepted for publication April 5, 2003.

Camilleri  MThompson  WGFleshman  JWPemberton  JH Clinical management of intractable constipation. Ann Intern Med. 1994;121520- 528
PubMed Link to Article
Locke  GR The epidemiology of functional gastrointestinal disorders in North America. Gastroenterol Clin North Am. 1996;251- 19
PubMed Link to Article
Locke  GRPemberton  JHPhillips  SF AGA technical review on constipation. Gastroenterology. 2000;1191766- 1778
PubMed Link to Article
van der Sijp  JRMKamm  MANightingale  JMD  et al.  Radioisotope determination of regional colonic transit in severe constipation: comparison with radio-opaque markers. Gut. 1993;34402- 408
PubMed Link to Article
Nyam  DCPemberton  JHIlstrup  DMRath  DM Long-term results of surgery for chronic constipation. Dis Colon Rectum. 1997;40273- 279
PubMed Link to Article
Knowles  CHScott  MSLunniss  PJ Slow transit constipation: a disorder of pelvic autonomic nerves? Dig Dis Sci. 2001;46389- 401
PubMed Link to Article
Preston  DMLennard-Jones  JE Severe chronic constipation of young women: "idiopathic slow transit constipation." Br J Surg. 1986;2741- 48
Roe  AMBartolo  DCCMortensen  NJ Slow transit constipation: comparison between patients with or without previous hysterectomy. Dig Dis Sci. 1988;331159- 1163
Link to Article
MacDonald  ABaxter  JNFinlay  IG Idiopathic slow-transit constipation. Br J Surg. 1993;801107- 1111
PubMed Link to Article
Miller  RDuthie  GSBartolo  DCCRoe  AMLocke-Edmunds  JMortenson  NJ Anismus in patients with normal and slow transit constipation. Br J Surg. 1991;78690- 692
PubMed Link to Article
Ferrara  APemberton  JHGrotz  RLHanson  RB Prolonged ambulatory recording of anorectal motility in patients with slow-transit constipation. Am J Surg. 1994;16773- 79
PubMed Link to Article
Rao  SSCSadeghi  PBatterson  KBeaty  J Altered periodic rectal motor activity: a mechanism for slow transit constipation. Neurogastroenterol Mot. 2001;13591- 598
Link to Article
Kamm  MALennard-Jones  JEThompson  DGSobnack  RGarvie  NWGranowska  M Dynamic scanning defines a colonic defect in severe idiopathic constipation. Gut. 1988;291085- 1092
PubMed Link to Article
Bassotti  GChiarioni  GVantini  IFusaro  CPelli  MAMorelli  A Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation. Dig Dis Sci. 1994;391558- 1564
PubMed Link to Article
Stivland  TCamilleri  MVassallo  M  et al.  Scintigraphic measurement of regional gut transit in idiopathic chronic constipation. Gastroenterology. 1991;101107- 115
PubMed
Thompson  WGLongstreth  GFDrossman  DAHeaton  KWIrvine  EJMuller-Lissner  SA Functional bowel disorders and functional abdominal pain. Gut. 1999;45 ((suppl II)) II43- II47
PubMed
Bassotti  GGaburri  MImbimbo  BP  et al.  Colonic mass movements in idiopathic chronic constipation. Gut. 1988;291173- 1179
PubMed Link to Article
Leroi  AMLalaude  OAntonietti  M  et al.  Prolonged stationary colonic motility recording in seven patients with severe constipation secondary to antidepressants. Neurogastroenterol Mot. 2000;12149- 154
Link to Article
Bassotti  G Motions and emotions: the treatment of depression causes constipation. Neurogastroenterol Mot. 2000;12113- 115
Link to Article
Phillips  SFPemberton  JH Megacolon: congenital and acquired. Feldman  MScharschmidt  BFSleisenger  MHeds.Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa WB Saunders Co1998;1810- 1819
Soffer  EEKongara  KAckar  JPGannon  J Colonic motor function in humans is not affected by gender. Dig Dis Sci. 2000;451281- 1284
PubMed Link to Article
Rao  SSSadeghi  PBeaty  JKavlock  RAckerson  K Ambulatory 24-h colonic manometry in healthy humans. Am J Physiol Gastrointest Liver Physiol. 2001;28G629- G639
Narducci  FBassotti  GGaburri  MMorelli  A Twenty four hour manometric recording of colonic motor activity in healthy man. Gut. 1987;2817- 25
PubMed Link to Article
Bassotti  GGaburri  M Manometric investigation of high-amplitude propagated contractile activity of the human colon. Am J Physiol. 1988;255G660- G664
Bassotti  GBetti  CFusaro  CMorelli  A Colonic high-amplitude propagated contractions (mass movements): repeated 24-h manometric studies in healthy volunteers. J Gastrointest Motility. 1992;84118- 122
Bassotti  GBetti  CImbimbo  BPPelli  MAMorelli  A Colonic motor response to eating: a manometric investigation in proximal and distal portions of the viscus in man. Am J Gastroenterol. 1989;84118- 122
PubMed
Crowell  MDBassotti  GCheskin  LJSchuster  MMWhitehead  WE Method for prolonged ambulatory monitoring of high-amplitude propagated contractions from colon. Am J Physiol. 1991;261G263- G268
PubMed
Bassotti  GClementi  MAntonelli  EPelli  MATonini  M Low-amplitude propagated contractile waves: a relevant propulsive mechanism of the human colon. Dig Liver Dis. 2001;3336- 40
PubMed Link to Article
Knowles  CHMartin  JE Slow transit constipation: a model of human gut dysmotility: review of possible aetiologies. Neurogastroenterol Mot. 2000;12181- 196
Link to Article
Cook  IJFurukawa  YPanagopoulos  VCollins  PJDent  J Relationships between spatial patterns of colonic pressure and individual movements of contents. Am J Physiol. 2000;278G329- G341
Schiller  LR Review article: the therapy of constipation. Aliment Pharmacol Ther. 2001;15749- 763
PubMed Link to Article
Wexner  SDDaniel  NJagelman  DG Colectomy for constipation: physiologic investigations is the key to success. Dis Colon Rectum. 1991;34851- 856
PubMed Link to Article
Pemberton  JHRath  DMIlstrup  DM Evaluation and surgical treatment of severe chronic constipation. Ann Surg. 1991;214403- 413
PubMed Link to Article
Bassotti  GBetti  CPelli  MAMorelli  A Extensive investigation on colonic motility with pharmacological testing is useful for selecting surgical options in patients with inertia colica. Am J Gastroenterology. 1992;87143- 147

Figures

Tables

Table Graphic Jump LocationHAPC and LAPC Variable in Patients With Slow-Transit Constipation and Controls*

References

Camilleri  MThompson  WGFleshman  JWPemberton  JH Clinical management of intractable constipation. Ann Intern Med. 1994;121520- 528
PubMed Link to Article
Locke  GR The epidemiology of functional gastrointestinal disorders in North America. Gastroenterol Clin North Am. 1996;251- 19
PubMed Link to Article
Locke  GRPemberton  JHPhillips  SF AGA technical review on constipation. Gastroenterology. 2000;1191766- 1778
PubMed Link to Article
van der Sijp  JRMKamm  MANightingale  JMD  et al.  Radioisotope determination of regional colonic transit in severe constipation: comparison with radio-opaque markers. Gut. 1993;34402- 408
PubMed Link to Article
Nyam  DCPemberton  JHIlstrup  DMRath  DM Long-term results of surgery for chronic constipation. Dis Colon Rectum. 1997;40273- 279
PubMed Link to Article
Knowles  CHScott  MSLunniss  PJ Slow transit constipation: a disorder of pelvic autonomic nerves? Dig Dis Sci. 2001;46389- 401
PubMed Link to Article
Preston  DMLennard-Jones  JE Severe chronic constipation of young women: "idiopathic slow transit constipation." Br J Surg. 1986;2741- 48
Roe  AMBartolo  DCCMortensen  NJ Slow transit constipation: comparison between patients with or without previous hysterectomy. Dig Dis Sci. 1988;331159- 1163
Link to Article
MacDonald  ABaxter  JNFinlay  IG Idiopathic slow-transit constipation. Br J Surg. 1993;801107- 1111
PubMed Link to Article
Miller  RDuthie  GSBartolo  DCCRoe  AMLocke-Edmunds  JMortenson  NJ Anismus in patients with normal and slow transit constipation. Br J Surg. 1991;78690- 692
PubMed Link to Article
Ferrara  APemberton  JHGrotz  RLHanson  RB Prolonged ambulatory recording of anorectal motility in patients with slow-transit constipation. Am J Surg. 1994;16773- 79
PubMed Link to Article
Rao  SSCSadeghi  PBatterson  KBeaty  J Altered periodic rectal motor activity: a mechanism for slow transit constipation. Neurogastroenterol Mot. 2001;13591- 598
Link to Article
Kamm  MALennard-Jones  JEThompson  DGSobnack  RGarvie  NWGranowska  M Dynamic scanning defines a colonic defect in severe idiopathic constipation. Gut. 1988;291085- 1092
PubMed Link to Article
Bassotti  GChiarioni  GVantini  IFusaro  CPelli  MAMorelli  A Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation. Dig Dis Sci. 1994;391558- 1564
PubMed Link to Article
Stivland  TCamilleri  MVassallo  M  et al.  Scintigraphic measurement of regional gut transit in idiopathic chronic constipation. Gastroenterology. 1991;101107- 115
PubMed
Thompson  WGLongstreth  GFDrossman  DAHeaton  KWIrvine  EJMuller-Lissner  SA Functional bowel disorders and functional abdominal pain. Gut. 1999;45 ((suppl II)) II43- II47
PubMed
Bassotti  GGaburri  MImbimbo  BP  et al.  Colonic mass movements in idiopathic chronic constipation. Gut. 1988;291173- 1179
PubMed Link to Article
Leroi  AMLalaude  OAntonietti  M  et al.  Prolonged stationary colonic motility recording in seven patients with severe constipation secondary to antidepressants. Neurogastroenterol Mot. 2000;12149- 154
Link to Article
Bassotti  G Motions and emotions: the treatment of depression causes constipation. Neurogastroenterol Mot. 2000;12113- 115
Link to Article
Phillips  SFPemberton  JH Megacolon: congenital and acquired. Feldman  MScharschmidt  BFSleisenger  MHeds.Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa WB Saunders Co1998;1810- 1819
Soffer  EEKongara  KAckar  JPGannon  J Colonic motor function in humans is not affected by gender. Dig Dis Sci. 2000;451281- 1284
PubMed Link to Article
Rao  SSSadeghi  PBeaty  JKavlock  RAckerson  K Ambulatory 24-h colonic manometry in healthy humans. Am J Physiol Gastrointest Liver Physiol. 2001;28G629- G639
Narducci  FBassotti  GGaburri  MMorelli  A Twenty four hour manometric recording of colonic motor activity in healthy man. Gut. 1987;2817- 25
PubMed Link to Article
Bassotti  GGaburri  M Manometric investigation of high-amplitude propagated contractile activity of the human colon. Am J Physiol. 1988;255G660- G664
Bassotti  GBetti  CFusaro  CMorelli  A Colonic high-amplitude propagated contractions (mass movements): repeated 24-h manometric studies in healthy volunteers. J Gastrointest Motility. 1992;84118- 122
Bassotti  GBetti  CImbimbo  BPPelli  MAMorelli  A Colonic motor response to eating: a manometric investigation in proximal and distal portions of the viscus in man. Am J Gastroenterol. 1989;84118- 122
PubMed
Crowell  MDBassotti  GCheskin  LJSchuster  MMWhitehead  WE Method for prolonged ambulatory monitoring of high-amplitude propagated contractions from colon. Am J Physiol. 1991;261G263- G268
PubMed
Bassotti  GClementi  MAntonelli  EPelli  MATonini  M Low-amplitude propagated contractile waves: a relevant propulsive mechanism of the human colon. Dig Liver Dis. 2001;3336- 40
PubMed Link to Article
Knowles  CHMartin  JE Slow transit constipation: a model of human gut dysmotility: review of possible aetiologies. Neurogastroenterol Mot. 2000;12181- 196
Link to Article
Cook  IJFurukawa  YPanagopoulos  VCollins  PJDent  J Relationships between spatial patterns of colonic pressure and individual movements of contents. Am J Physiol. 2000;278G329- G341
Schiller  LR Review article: the therapy of constipation. Aliment Pharmacol Ther. 2001;15749- 763
PubMed Link to Article
Wexner  SDDaniel  NJagelman  DG Colectomy for constipation: physiologic investigations is the key to success. Dis Colon Rectum. 1991;34851- 856
PubMed Link to Article
Pemberton  JHRath  DMIlstrup  DM Evaluation and surgical treatment of severe chronic constipation. Ann Surg. 1991;214403- 413
PubMed Link to Article
Bassotti  GBetti  CPelli  MAMorelli  A Extensive investigation on colonic motility with pharmacological testing is useful for selecting surgical options in patients with inertia colica. Am J Gastroenterology. 1992;87143- 147

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