Letters to Editor
patients to develop thrombocytopenia, like subclinical disseminated intravascular coagulation to paraneoplastic thrombocytopenia. There are multiple drugs, which can induce immune and non-immune thrombocytopenia including anticancer drugs. In reference patient, bone marrow, anti-nuclear antibody, urine for proteins, ultrasonography abdomen as a protocol for evaluation of thrombocytopenia was not done. The patient presented was on capecitabine, drug used in colonic cancer, which can have profound effect on platelets to cause significant thrombocytopenia.[6] Another issue we want to address is to desist from platelet transfusion in any unexplained thrombocytopenia. It is relatively contraindicated not only in HIT, but any immune thrombocytopenia such as Idiopathic thrombocytopenic purpura or thrombotic thrombocytopenic purpura, which occur more commonly than HIT. Lastly, if a diagnosis of HIT is made and which should be kept as a possibility in a patient on heparin, a term like unexplained thrombocytopenia should not be used.
REFERENCES 1. Chong BH, Castaldi PA. Platelet proaggregating effect of heparin: Possible mechanism for non-immune heparinassociated thrombocytopenia. Aust N Z J Med 1986;16:715-6. 2. Greinacher A. Antigen generation in heparin-associated thrombocytopenia: The nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Hemost 1995;21:106-16. 3. Warkentin TE, Greinacher A, Koster A, Lincoff AM, American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:340S-8. 4. Stanton PE Jr, Evans JR, Lefemine AA, Vo NM, Rannick GA, Morgan CV Jr, et al. White clot syndrome. South Med J 1988;81:616-20. 5. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecularweight heparin thromboprophylaxis: A meta-analysis. Blood 2005;106:2710-5. 6. Mercier C, Ciccolini J. Severe or lethal toxicities upon capecitabine intake: Is DPYD genetic polymorphism the ideal culprit? Trends Pharmacol Sci 2007;28:597-8. Access this article online Quick Response Code:
Website: www.ijmpo.org
Ajaz Nabi Koul, Ridwana Ahad1 Departments of Internal Medicine and 1Community Medicine, SKIMS, Srinagar, Jammu and Kashmir, India. E-mail: [email protected]
DOI: 10.4103/0971-5851.125267
Sedation and analgesia during bone marrow aspiration in children: Is ketamine and propofol combination (Ketofol) an appropriate agent? Sir, Multiple bone marrow aspiration (BMA) and lumbar puncture (LP) is an essential diagnostic approach to the diagnosis of hematological disorders, which is performed on children with leukemia and other neoplastic disorders during the course of their illnesses. These invasive procedures can lead to considerable pain and distress in children, which is considered by the patients as the most painful experience relating to their malignancy.[1,2] Therefore, in these procedures, pain management is now considered an essential part of care in children with cancer.[3] Regimes for the optimal pain management in these children vary widely. Usually before these procedures, local anesthetic (LA) is used to numb the area and reduce pain. The patients may also receive intravenous sedation (IVS)
and analgesia.[1] It has been shown that patients receiving IVS have a lower pain score and tend to have lower levels of apprehension at the thought of having a repeat procedure. This is important because in many cases, these procedures are frequently repeated.[3,4] Therefore, an adequate sedation and analgesia is essential in these procedures. An ideal agent for procedural sedation should not only have quick onset and recovery time but also provide satisfactory analgesia, sedation while maintaining cardiopulmonary homeostasis, amnesia, and motor control throughout the procedure. Although many pharmacological agents have some of these qualities, none possess all of them and consequently physicians must use combinations of different drugs at varying doses to achieve as many of the preferred goals as possible.[5,6] Propofol, a popular sedative of choice for procedural sedation, is a short-acting non-opioid, non-
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
337
Letters to Editor
barbiturate, and sedative-hypnotic agent with rapid onset and short duration of action. It possesses antiemetic effects and reliably produces sedation.[5] Its adverse effects include dose-related respiratory and cardiovascular depression and bradycardia. Propofol is known to be amnestic, but lacks analgesic effect and, therefore, is commonly combined with an analgesic agent.[5-7] Ketamine is a fast-acting dissociative anesthetic that produces a profound analgesic effect. It causes little or no respiratory or cardiovascular depression, and due to its cardiostimulatory effects and strong safety profile, has gained favor for procedural sedation and analgesia in children,[8] although it has some drawbacks such as the incidence of emergence reactions at increasing doses, which may include nightmares or vivid hallucinations.[5] In theory, the opposing hemodynamic and respiratory effects of these drugs might be complementary and minimize the overall adverse effects. The use of ketamine in combination with propofol (Ketofol) has been shown to decrease the dose of propofol required to achieve sedation, and is believed to result in less toxicity than that caused when either drug is used alone, because their complementary effects enable the use of lower doses of each drug.[7] Since Ketofol is a relatively new idea for most medical practitioners, there is little in the scientific literature on its use for procedural sedation and analgesia during BMA and LP in children, although its clinical efficacy for pediatric sedation in other situations such as in emergency department and pediatric orthopedic surgery has previously been described.[8-11] In a study by da Silva et al. conducted with an aim to evaluate the safety and effectiveness of Ketofol (1:1 mixture of ketamine 10 mg/ml and propofol 10 mg/ml) for procedural sedation and analgesia in children undergoing BMA, it was observed that Ketofol provides effective sedation (reflected in the high degree of satisfaction recorded by the children) and also rapid recovery with no clinically significant complications.[5] In another study by Hashemi et al. conducted with an aim to compare the efficacy, respiratory and hemodynamic profiles, and the side effects of two various doses of Ketofol, equal amount of propofol and ketamine (1:1) or two parts of propofol plus one part of ketamine (2:1), in children with acute lymphoblastic leukemia (ALL) undergoing BMA and LP, it was observed that although sedation scores in both groups were similar, there was increased postoperative nausea, psychomimetic side effects, and increase in recovery time with the largest ketamine dosage. Therefore, it was concluded that the adjunctive use of smaller dose of ketamine in Ketofol combination minimizes the psychomimetic side effects and shortens the recovery time.[12] Ghadami Yazdi et al. in a randomized clinical trial conducted with an aim to compare two different combinations of Ketofol, one part of ketamine and two parts of propofol (1:2) or one part of ketamine and three parts of propofol (1:3), to reach necessary sedation 338
scale for the LP or BMA in pediatric patients with ALL, it was observed that lower doses of ketamine in these combinations caused lower psychomimetic side effects and shorter recovery time.[13] In another study by Daabiss et al. performed with an aim to compare the quality of analgesia and side effects of intravenous varying concentrations of Ketofol, admixture of propofol:ketamine (1:1) or propofol:ketamine (4:1), in children undergoing procedural operations including BMA, esophagoscopy, rectoscopy, and liver biopsy, it was observed that there were no significant hemodynamic changes in both groups of children. It was concluded that adjunctive use of smaller dose of ketamine in Ketofol combination minimizes the psychomimetic side effects and shortens the time to discharge.[14] In summary, considering the importance of pain management in children undergoing BMA and also analyzing the results from the recent studies about the use of Ketofol as an effective agent for procedural sedation and analgesia during BMA in children, it seems that propofol– ketamine combination (Ketofol) can be used as a safe and appropriate agent for procedural sedation and analgesia during BMA, although further clinical trials are required to identify the effectiveness of Ketofol as well as the optimum dose of ketamine and propofol in combination for these patients. Mohammad Reza Habibi, Farshad Hasanzadeh Kiabi, Aria Soleimani, Amir Emami Zeydi1 Department of Anesthesiology, Faculty of Medicine, Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, 1PhD Student in Nursing, Faculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran E-mail: [email protected]
References 1. Crock C, Olsson C, Phillips R, Chalkiadis G, Sawyer S, Ashley D, et al. General anaesthesia or conscious sedation for painful procedures in childhood cancer: The family’s perspective. Arch Dis Child 2003;88:253-7. 2. Hedström M, Haglund K, Skolin I, von Essen L. Distressing events for children and adolescents with cancer: Child, parent, and nurse perceptions. J Pediatr Oncol Nurs 2003;20:120-32. 3. Hjortholm N, Jaddini E, Hałaburda K, Snarski E. Strategies of pain reduction during the bone marrow biopsy. Ann Hematol 2013;92:145-9. 4. Giannoutsos I, Grech H, Maboreke T, Morgenstern G. Performing bone marrow biopsies with or without sedation: A comparison. Clin Lab Haematol 2004;26:201-4. 5. da Silva PS, de Aguiar VE, Waisberg DR, Passos RM, Park MV. Use of ketofol for procedural sedation and analgesia in children with hematological diseases. Pediatr Int 2011;53:62-7. 6. Evered LM. Procedural sedation and analgesia for paediatric patients in the emergency department. Paediatr Child Health 2003;8:503-7.
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
Letters to Editor 7. Willman EV, Andolfatto G. A prospective evaluation of “ketofol” (ketamine/propofol combination) for procedural sedation and analgesia in the emergency department. Ann Emerg Med 2007;49:23-30. 8. Brown TB, Lovato LM, Parker D. Procedural sedation in the acute care setting. Am Fam Physician 2005;71:85-90. 9. Weatherall A, Venclovas R. Experience with a propofol– ketamine mixture for sedation during pediatric orthopedic surgery. Paediatr Anaesth 2010;20:1009-16. 10. Andolfatto G, Willman E. A prospective case series of pediatric procedural sedation and analgesia in the emergency department using single-syringe ketamine–propofol combination (ketofol). Acad Emerg Med 2010;17:194-201. 11. Andolfatto G, Abu-Laban RB, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, et al. Ketamine–propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia: A randomized double-blind trial. Ann Emerg Med 2012;59:504-12.e1-2. 12. Hashemi A, Ayatolahi V, Ghilian R, Ghadami Yazdi A, Fadavi N, Yadegar Y, et al. Ketofol for bone marrow aspiration
and lumbar puncture in children with ALL. Iran J Ped Hematol Oncol 2011;1:126-32. 13. Ghadami Yazdi A, Ayatollahi V, Hashemi A, Behdad SH, Ghadami Yazdi E. Effect of two different concentrations of propofol and ketamine combinations (Ketofol) in pediatric patients under lumbar puncture or bone marrow aspiration. Iran J Ped Hematol Oncol 2013;3:11-6. 14. Daabiss M, Elsherbiny M, Alotibi R. Assessment of different concentrations of ketofol in procedural operation. Br J Med Practitioners 2009;2:27-31. Access this article online Quick Response Code:
Website: www.ijmpo.org
DOI: 10.4103/0971-5851.125268
Author Institution Mapping (AIM)
Please note that not all the institutions may get mapped due to non-availability of the requisite information in the Google Map. For AIM of other issues, please check the Archives/Back Issues page on the journal’s website.
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
339
Copyright of Indian Journal of Medical & Paediatric Oncology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
patients to develop thrombocytopenia, like subclinical disseminated intravascular coagulation to paraneoplastic thrombocytopenia. There are multiple drugs, which can induce immune and non-immune thrombocytopenia including anticancer drugs. In reference patient, bone marrow, anti-nuclear antibody, urine for proteins, ultrasonography abdomen as a protocol for evaluation of thrombocytopenia was not done. The patient presented was on capecitabine, drug used in colonic cancer, which can have profound effect on platelets to cause significant thrombocytopenia.[6] Another issue we want to address is to desist from platelet transfusion in any unexplained thrombocytopenia. It is relatively contraindicated not only in HIT, but any immune thrombocytopenia such as Idiopathic thrombocytopenic purpura or thrombotic thrombocytopenic purpura, which occur more commonly than HIT. Lastly, if a diagnosis of HIT is made and which should be kept as a possibility in a patient on heparin, a term like unexplained thrombocytopenia should not be used.
REFERENCES 1. Chong BH, Castaldi PA. Platelet proaggregating effect of heparin: Possible mechanism for non-immune heparinassociated thrombocytopenia. Aust N Z J Med 1986;16:715-6. 2. Greinacher A. Antigen generation in heparin-associated thrombocytopenia: The nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Hemost 1995;21:106-16. 3. Warkentin TE, Greinacher A, Koster A, Lincoff AM, American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:340S-8. 4. Stanton PE Jr, Evans JR, Lefemine AA, Vo NM, Rannick GA, Morgan CV Jr, et al. White clot syndrome. South Med J 1988;81:616-20. 5. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecularweight heparin thromboprophylaxis: A meta-analysis. Blood 2005;106:2710-5. 6. Mercier C, Ciccolini J. Severe or lethal toxicities upon capecitabine intake: Is DPYD genetic polymorphism the ideal culprit? Trends Pharmacol Sci 2007;28:597-8. Access this article online Quick Response Code:
Website: www.ijmpo.org
Ajaz Nabi Koul, Ridwana Ahad1 Departments of Internal Medicine and 1Community Medicine, SKIMS, Srinagar, Jammu and Kashmir, India. E-mail: [email protected]
DOI: 10.4103/0971-5851.125267
Sedation and analgesia during bone marrow aspiration in children: Is ketamine and propofol combination (Ketofol) an appropriate agent? Sir, Multiple bone marrow aspiration (BMA) and lumbar puncture (LP) is an essential diagnostic approach to the diagnosis of hematological disorders, which is performed on children with leukemia and other neoplastic disorders during the course of their illnesses. These invasive procedures can lead to considerable pain and distress in children, which is considered by the patients as the most painful experience relating to their malignancy.[1,2] Therefore, in these procedures, pain management is now considered an essential part of care in children with cancer.[3] Regimes for the optimal pain management in these children vary widely. Usually before these procedures, local anesthetic (LA) is used to numb the area and reduce pain. The patients may also receive intravenous sedation (IVS)
and analgesia.[1] It has been shown that patients receiving IVS have a lower pain score and tend to have lower levels of apprehension at the thought of having a repeat procedure. This is important because in many cases, these procedures are frequently repeated.[3,4] Therefore, an adequate sedation and analgesia is essential in these procedures. An ideal agent for procedural sedation should not only have quick onset and recovery time but also provide satisfactory analgesia, sedation while maintaining cardiopulmonary homeostasis, amnesia, and motor control throughout the procedure. Although many pharmacological agents have some of these qualities, none possess all of them and consequently physicians must use combinations of different drugs at varying doses to achieve as many of the preferred goals as possible.[5,6] Propofol, a popular sedative of choice for procedural sedation, is a short-acting non-opioid, non-
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
337
Letters to Editor
barbiturate, and sedative-hypnotic agent with rapid onset and short duration of action. It possesses antiemetic effects and reliably produces sedation.[5] Its adverse effects include dose-related respiratory and cardiovascular depression and bradycardia. Propofol is known to be amnestic, but lacks analgesic effect and, therefore, is commonly combined with an analgesic agent.[5-7] Ketamine is a fast-acting dissociative anesthetic that produces a profound analgesic effect. It causes little or no respiratory or cardiovascular depression, and due to its cardiostimulatory effects and strong safety profile, has gained favor for procedural sedation and analgesia in children,[8] although it has some drawbacks such as the incidence of emergence reactions at increasing doses, which may include nightmares or vivid hallucinations.[5] In theory, the opposing hemodynamic and respiratory effects of these drugs might be complementary and minimize the overall adverse effects. The use of ketamine in combination with propofol (Ketofol) has been shown to decrease the dose of propofol required to achieve sedation, and is believed to result in less toxicity than that caused when either drug is used alone, because their complementary effects enable the use of lower doses of each drug.[7] Since Ketofol is a relatively new idea for most medical practitioners, there is little in the scientific literature on its use for procedural sedation and analgesia during BMA and LP in children, although its clinical efficacy for pediatric sedation in other situations such as in emergency department and pediatric orthopedic surgery has previously been described.[8-11] In a study by da Silva et al. conducted with an aim to evaluate the safety and effectiveness of Ketofol (1:1 mixture of ketamine 10 mg/ml and propofol 10 mg/ml) for procedural sedation and analgesia in children undergoing BMA, it was observed that Ketofol provides effective sedation (reflected in the high degree of satisfaction recorded by the children) and also rapid recovery with no clinically significant complications.[5] In another study by Hashemi et al. conducted with an aim to compare the efficacy, respiratory and hemodynamic profiles, and the side effects of two various doses of Ketofol, equal amount of propofol and ketamine (1:1) or two parts of propofol plus one part of ketamine (2:1), in children with acute lymphoblastic leukemia (ALL) undergoing BMA and LP, it was observed that although sedation scores in both groups were similar, there was increased postoperative nausea, psychomimetic side effects, and increase in recovery time with the largest ketamine dosage. Therefore, it was concluded that the adjunctive use of smaller dose of ketamine in Ketofol combination minimizes the psychomimetic side effects and shortens the recovery time.[12] Ghadami Yazdi et al. in a randomized clinical trial conducted with an aim to compare two different combinations of Ketofol, one part of ketamine and two parts of propofol (1:2) or one part of ketamine and three parts of propofol (1:3), to reach necessary sedation 338
scale for the LP or BMA in pediatric patients with ALL, it was observed that lower doses of ketamine in these combinations caused lower psychomimetic side effects and shorter recovery time.[13] In another study by Daabiss et al. performed with an aim to compare the quality of analgesia and side effects of intravenous varying concentrations of Ketofol, admixture of propofol:ketamine (1:1) or propofol:ketamine (4:1), in children undergoing procedural operations including BMA, esophagoscopy, rectoscopy, and liver biopsy, it was observed that there were no significant hemodynamic changes in both groups of children. It was concluded that adjunctive use of smaller dose of ketamine in Ketofol combination minimizes the psychomimetic side effects and shortens the time to discharge.[14] In summary, considering the importance of pain management in children undergoing BMA and also analyzing the results from the recent studies about the use of Ketofol as an effective agent for procedural sedation and analgesia during BMA in children, it seems that propofol– ketamine combination (Ketofol) can be used as a safe and appropriate agent for procedural sedation and analgesia during BMA, although further clinical trials are required to identify the effectiveness of Ketofol as well as the optimum dose of ketamine and propofol in combination for these patients. Mohammad Reza Habibi, Farshad Hasanzadeh Kiabi, Aria Soleimani, Amir Emami Zeydi1 Department of Anesthesiology, Faculty of Medicine, Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, 1PhD Student in Nursing, Faculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran E-mail: [email protected]
References 1. Crock C, Olsson C, Phillips R, Chalkiadis G, Sawyer S, Ashley D, et al. General anaesthesia or conscious sedation for painful procedures in childhood cancer: The family’s perspective. Arch Dis Child 2003;88:253-7. 2. Hedström M, Haglund K, Skolin I, von Essen L. Distressing events for children and adolescents with cancer: Child, parent, and nurse perceptions. J Pediatr Oncol Nurs 2003;20:120-32. 3. Hjortholm N, Jaddini E, Hałaburda K, Snarski E. Strategies of pain reduction during the bone marrow biopsy. Ann Hematol 2013;92:145-9. 4. Giannoutsos I, Grech H, Maboreke T, Morgenstern G. Performing bone marrow biopsies with or without sedation: A comparison. Clin Lab Haematol 2004;26:201-4. 5. da Silva PS, de Aguiar VE, Waisberg DR, Passos RM, Park MV. Use of ketofol for procedural sedation and analgesia in children with hematological diseases. Pediatr Int 2011;53:62-7. 6. Evered LM. Procedural sedation and analgesia for paediatric patients in the emergency department. Paediatr Child Health 2003;8:503-7.
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
Letters to Editor 7. Willman EV, Andolfatto G. A prospective evaluation of “ketofol” (ketamine/propofol combination) for procedural sedation and analgesia in the emergency department. Ann Emerg Med 2007;49:23-30. 8. Brown TB, Lovato LM, Parker D. Procedural sedation in the acute care setting. Am Fam Physician 2005;71:85-90. 9. Weatherall A, Venclovas R. Experience with a propofol– ketamine mixture for sedation during pediatric orthopedic surgery. Paediatr Anaesth 2010;20:1009-16. 10. Andolfatto G, Willman E. A prospective case series of pediatric procedural sedation and analgesia in the emergency department using single-syringe ketamine–propofol combination (ketofol). Acad Emerg Med 2010;17:194-201. 11. Andolfatto G, Abu-Laban RB, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, et al. Ketamine–propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia: A randomized double-blind trial. Ann Emerg Med 2012;59:504-12.e1-2. 12. Hashemi A, Ayatolahi V, Ghilian R, Ghadami Yazdi A, Fadavi N, Yadegar Y, et al. Ketofol for bone marrow aspiration
and lumbar puncture in children with ALL. Iran J Ped Hematol Oncol 2011;1:126-32. 13. Ghadami Yazdi A, Ayatollahi V, Hashemi A, Behdad SH, Ghadami Yazdi E. Effect of two different concentrations of propofol and ketamine combinations (Ketofol) in pediatric patients under lumbar puncture or bone marrow aspiration. Iran J Ped Hematol Oncol 2013;3:11-6. 14. Daabiss M, Elsherbiny M, Alotibi R. Assessment of different concentrations of ketofol in procedural operation. Br J Med Practitioners 2009;2:27-31. Access this article online Quick Response Code:
Website: www.ijmpo.org
DOI: 10.4103/0971-5851.125268
Author Institution Mapping (AIM)
Please note that not all the institutions may get mapped due to non-availability of the requisite information in the Google Map. For AIM of other issues, please check the Archives/Back Issues page on the journal’s website.
Indian Journal of Medical and Paediatric Oncology | Oct-Dec 2013 | Vol 34 | Issue 4
339
Copyright of Indian Journal of Medical & Paediatric Oncology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
