Management of Labor Analgesia in a Patient with Acute Myeloid Leukemia Kelly G. Elterman, MD,* Jonathan R. Meserve, MD,* Martha Wadleigh, MD,† Michaela K. Farber, MD,* and Lawrence C. Tsen, MD* The anesthetic implications of acute leukemia in pregnancy have not been reported. We describe the anesthetic management of a laboring primigravida at 34 weeks’ gestation with new-onset acute myeloid leukemia. With multidisciplinary consultation, we recommend that neuraxial anesthesia be avoided in new-onset acute myeloid leukemia due to the risk of introducing malignant cells into the central nervous system, which can spread the disease and complicate management. We discuss the use of a fentanyl patient-controlled analgesia and dexmedetomidine as a method of labor analgesia, and the potential benefits of the latter medication in the obstetric population. (A&A Case Reports. 2014;3:104–6.)
N
ewly diagnosed acute leukemia in pregnancy is a rare and challenging event, the management of which warrants collaboration among hematologists, obstetricians, and anesthesiologists. The incidence of acute leukemia in pregnancy is estimated to be 1 in 75,000 to 100,000 pregnancies.1 Acute myeloid leukemia (AML) is the most common acute leukemia in pregnancy, accounting for more than two-thirds of all cases.2 Most frequently detected in the second and third trimesters,2 acute leukemia in pregnancy presents unique challenges for the health care team; the timing and mode of delivery relative to initiation of chemotherapy with resulting pancytopenia as well as the decisions regarding analgesic or anesthetic management require an analysis of the maternal and fetal risks and benefits. We present our anesthetic management of a patient with newly diagnosed AML for whom neuraxial analgesia was contraindicated due to the presence of circulating leukemic blast cells. Written consent was obtained from the patient to publish this report.
CASE DESCRIPTION
A 32-year-old primigravida at 34 weeks’ gestation was admitted for leukocytosis, thrombocytopenia, and a peripheral blood smear with suspected blast (abnormal immature white blood cell) forms. Leukocytosis was detected on routine blood work in her first trimester with subsequent resolution on repeat evaluation. A hematologic consultation had been recommended but not pursued. At 33 weeks’ gestation, the patient complained of diffuse musculoskeletal pain refractory to muscle relaxants and opioid analgesics. After repeated pain evaluations by her local physician and the emergency department, routine blood work revealed From the *Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and †Hematology– Oncology, Dana Farber Cancer Institute/Brigham and Women’s Hospital, Boston, Massachusetts. Accepted for publication May 1, 2014. Funding: None. The authors declare no conflicts of interest. Address correspondence to Kelly G. Elterman, MD, Brigham and Women’s Hospital, 75 Francis St., CWN-L1, Boston, MA 02115. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000076
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a prominent leukocytosis with new thrombocytopenia. Review of the peripheral blood smear demonstrated immature monocytic forms consistent with leukemic blasts. Upon admission, the patient reported several days of night sweats, progressive fatigue, gingival bleeding, and diffuse bone and muscle pain. Laboratory evaluation revealed leukocytosis (39,000/μL), thrombocytopenia (59,000/μL), and normochromic macrocytic anemia (hemoglobin: 10.1 g/dL; mean corpuscular volume: 103.8 μm3). A peripheral smear revealed abundant monocytic forms in all stages of maturation with rare blast forms indicative of acute monocytic leukemia. The patient underwent an immediate bone marrow biopsy, and preliminary flow cytometry revealed AML with monocytic features. A multidisciplinary meeting with the patient, her family, and the relevant health care teams (obstetrics, obstetric anesthesia, and hematology/oncology) determined that urgent delivery would be necessary to enable the induction of chemotherapy. Initial discussions focused on a cesarean delivery performed under spinal anesthesia; however, this approach was ultimately abandoned due to the potential for introduction of malignant cells into the central nervous system (CNS) and resultant increased complexity of disease management. General anesthesia was therefore determined to be the safest option if a cesarean delivery was required. The patient indicated a strong preference to avoid cesarean delivery and general anesthesia, and thus labor was induced with oxytocin with an anticipated vaginal delivery. Intravenous analgesic drugs were discussed with the patient. Contingency planning included an emergent cesarean delivery performed under general anesthesia, with the intraoperative placement of an ultrasound-guided triplelumen central venous catheter for the postpartum initiation of chemotherapy. Labor analgesia was requested and achieved in the first stage of labor with IV patient-controlled analgesia using fentanyl (13 mcg bolus, 7-minute lockout, 300 mcg/4 h maximal dose, no basal infusion). During the second stage of labor, the patient experienced breakthrough pain and requested additional analgesia. Dexmedetomidine 50 mcg (0.5 mcg/kg) was administered IV over 10 minutes, with sufficient analgesic effect for the remainder of the second stage of labor; the patient did not require additional medication. She experienced no hypotension, bradycardia, or October 15, 2014 • Volume 3 • Number 8
oxyhemoglobin desaturation (continuous pulse oximetry remained 98%–99% with 4 L oxygen face mask). Ninety minutes later, a healthy male neonate was delivered with 1- and 5-minute Apgar scores of 9 and 9, respectively.
DISCUSSION
Acute leukemia, either myeloid or lymphoid, is one of the most common malignancies to occur in pregnancy and should be treated immediately to optimize maternal prognosis.2 When diagnosed in the first trimester, patients are often advised to terminate the pregnancy due to the toxicity of chemotherapeutic drugs and the frequent need for stem cell transplantation.1 In the second and third trimesters, chemotherapy is often initiated because the risk of teratogenicity is decreased,3 but the timing of delivery and post-chemotherapeutic pancytopenia remain of concern. Importantly, the neurodevelopmental outcomes of children with intrauterine chemotherapy exposure appear no different than that of the general population.4,5 However, when the age of the fetus is closer to term, minimizing fetal chemotherapy exposure by early delivery is accepted as a prudent management strategy. The anesthetic management of a patient with chronic neutrophilic leukemia during pregnancy was recently reported,6 but to our knowledge the peripartum management of a patient with acute leukemia has not been described. While both acute and chronic leukemia may predispose patients to both hemorrhage and thrombosis,7 due to thrombocytopenia and the presence of malignancy, respectively, chronic leukemia does not typically present with thrombocytopenia until later stages.8 Thus, acute leukemia is more likely to present an unpredictable bleeding risk. Whether the presence of concurrent AML and pregnancy, itself a hypercoagulable state,9 increases the risk of venous thromboembolism has not been reported. However, other myelodysplastic conditions, such as essential thrombocytosis and polycythemia vera, present an increased risk for venous and arterial thrombosis with pregnancy.10 Patients with acute leukemia, or blast crisis phase of chronic leukemia, often present with severe thrombocytopenia, which enhances the risk for postpartum hemorrhage and increases the risk for epidural hematoma with neuraxial techniques. While there are no strict guidelines regarding a minimal platelet count necessary for a neuraxial technique, anesthesiologists often avoid neuraxial techniques in patients with platelet counts 10 red blood cells per microliter, had worse event-free survival than their counterparts
October 15, 2014 • Volume 3 • Number 8
without CNS disease. While the reasons for these worse outcomes are unclear, several groups have attributed the increased mortality to the introduction of hematogenously circulating blast cells into the cerebrospinal fluid at the time of lumbar puncture.11–14 Thus, while the risk of spinal anesthesia in the patient with untreated AML is unknown, these studies would suggest that resultant worsening of oncologic outcome is possible. Although the epidural technique per se should not increase this risk, inadvertent dural puncture occurs in approximately 0.19% to 3.6% of epidural techniques in laboring women.15 Due to these considerations, and in consultation with our obstetric and hematologic colleagues, we decided to manage labor analgesia with an IV fentanyl patient-controlled analgesia with dexmedetomidine for breakthrough pain relief. Although dexmedetomidine has received only limited clinical evaluation during pregnancy, when compared with clonidine, it has an 8-fold greater α-2 selectivity,16 less fetal transfer in an in vitro placental model,17 and minimal, if any, effects on fetal physiology during labor.18 Dexmedetomidine may also offer several benefits to obstetric patients. First, animal studies have demonstrated analgesic synergism between fentanyl and α-2 agonists.19 Additionally, while opioids and local anesthetics may decrease the effectiveness of in vitro uterine contractions,20 α-2 agonists have been observed in in vitro studies to increase the frequency and amplitude of human myometrial contractions.21 Although not currently approved for use during pregnancy, dexmedetomidine has been used successfully in parturients for labor analgesia,22 general anesthesia for cesarean delivery,22 and nonobstetric surgery.23
CONCLUSIONS
Our case illustrates the importance of a multidisciplinary approach to the pregnant patient with a newly diagnosed acute hematologic malignancy. While AML in pregnancy is rare, the risks of inadvertent CNS seeding and subsequent prognostic implications are relative contraindications to the performance of neuraxial techniques. E REFERENCES 1. Brenner B, Avivi I, Lishner M. Haematological cancers in pregnancy. Lancet 2012;379:580–7 2. Chelghoum Y, Vey N, Raffoux E, Huguet F, Pigneux A, Witz B, Pautas C, de Botton S, Guyotat D, Lioure B, Fegueux N, Garban F, Saad H, Thomas X. Acute leukemia during pregnancy: a report on 37 patients and a review of the literature. Cancer 2005;104:110–7 3. Selig BP, Furr JR, Huey RW, Moran C, Alluri VN, Medders GR, Mumm CD, Hallford HG, Mulvihill JJ. Cancer chemotherapeutic agents as human teratogens. Birth Defects Res A Clin Mol Teratol 2012;94:626–50 4. Avilés A, Neri N. Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. Clin Lymphoma 2001;2:173–7 5. Nulman I, Laslo D, Fried S, Uleryk E, Lishner M, Koren G. Neurodevelopment of children exposed in utero to treatment of maternal malignancy. Br J Cancer 2001;85:1611–8 6. Taylor J, Roboz GJ, Baergen RN, Genc MR. Pregnancy in a woman with chronic neutrophilic leukemia. Obstet Gynecol 2013;121:457–60 7. Kwaan HC. Double hazard of thrombophilia and bleeding in leukemia. Hematology Am Soc Hematol Educ Program 2007:151–7 8. Enright H, Bond J. Chronic leukemias. Dis Mon 2008;54:242–55 9. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003;16:153–68
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10. Barbui T, Finazzi G. Myeloproliferative disease in pregnancy and other management issues. Hematology Am Soc Hematol Educ Program 2006:246–52 11. Gajjar A, Harrison PL, Sandlund JT, Rivera GK, Ribeiro RC, Rubnitz JE, Razzouk B, Relling MV, Evans WE, Boyett JM, Pui CH. Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia. Blood 2000;96:3381–4 12. Bürger B, Zimmermann M, Mann G, Kühl J, Löning L, Riehm H, Reiter A, Schrappe M. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003;21:184–8 13. te Loo DM, Kamps WA, van der Does-van den Berg A, van Wering ER, de Graaf SS. Prognostic significance of blasts in the cerebrospinal fluid without pleiocytosis or a traumatic lumbar puncture in children with acute lymphoblastic leukemia: experience of the Dutch Childhood Oncology Group. J Clin Oncol 2006;24:2332–6 14. Kebelmann-Betzing C, Seeger K, Wolf R, Henze G. Traumatic lumbar puncture at diagnosis and outcome in childhood acute lymphoblastic leukemia. Blood 2001;98:3496–7 15. Heesen M, Klöhr S, Rossaint R, Van De Velde M, Straube S. Can the incidence of accidental dural puncture in laboring women be reduced? A systematic review and meta-analysis. Minerva Anestesiol 2013;79:1187–97 16. Coursin DB, Coursin DB, Maccioli GA. Dexmedetomidine. Curr Opin Crit Care 2001;7:221–6
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17. Ala-Kokko TI, Pienimäki P, Lampela E, Hollmén AI, Pelkonen O, Vähäkangas K. Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta. Acta Anaesthesiol Scand 1997;41:313–9 18. Uemura K, Shimazutsu K, McClaine RJ, McClaine DJ, Manson RJ, White WD, Benni PB, Reynolds JD. Maternal and preterm fetal sheep responses to dexmedetomidine. Int J Obstet Anesth 2012;21:339–47 19. Meert TF, De Kock M. Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats. Anesthesiology 1994;81:677–88 20. Nacitarhan C, Sadan G, Kayacan N, Ertugrul F, Arici G, Karsli B, Erman M. The effects of opioids, local anesthetics and adjuvants on isolated pregnant rat uterine muscles. Methods Find Exp Clin Pharmacol 2007;29:273–6 21. Sia AT, Kwek K, Yeo GS. The in vitro effects of clonidine and dexmedetomidine on human myometrium. Int J Obstet Anesth 2005;14:104–7 22. Palanisamy A, Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth 2009;18: 258–61 23. Souza KM, Anzoategui LC, Pedroso WC, Gemperli WA. [Dexmedetomidine in general anesthesia for surgical treatment of cerebral aneurysm in pregnant patient with specific hypertensive disease of pregnancy: case report.]. Rev Bras Anestesiol 2005;55:212–6
A & A case reports
N
ewly diagnosed acute leukemia in pregnancy is a rare and challenging event, the management of which warrants collaboration among hematologists, obstetricians, and anesthesiologists. The incidence of acute leukemia in pregnancy is estimated to be 1 in 75,000 to 100,000 pregnancies.1 Acute myeloid leukemia (AML) is the most common acute leukemia in pregnancy, accounting for more than two-thirds of all cases.2 Most frequently detected in the second and third trimesters,2 acute leukemia in pregnancy presents unique challenges for the health care team; the timing and mode of delivery relative to initiation of chemotherapy with resulting pancytopenia as well as the decisions regarding analgesic or anesthetic management require an analysis of the maternal and fetal risks and benefits. We present our anesthetic management of a patient with newly diagnosed AML for whom neuraxial analgesia was contraindicated due to the presence of circulating leukemic blast cells. Written consent was obtained from the patient to publish this report.
CASE DESCRIPTION
A 32-year-old primigravida at 34 weeks’ gestation was admitted for leukocytosis, thrombocytopenia, and a peripheral blood smear with suspected blast (abnormal immature white blood cell) forms. Leukocytosis was detected on routine blood work in her first trimester with subsequent resolution on repeat evaluation. A hematologic consultation had been recommended but not pursued. At 33 weeks’ gestation, the patient complained of diffuse musculoskeletal pain refractory to muscle relaxants and opioid analgesics. After repeated pain evaluations by her local physician and the emergency department, routine blood work revealed From the *Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and †Hematology– Oncology, Dana Farber Cancer Institute/Brigham and Women’s Hospital, Boston, Massachusetts. Accepted for publication May 1, 2014. Funding: None. The authors declare no conflicts of interest. Address correspondence to Kelly G. Elterman, MD, Brigham and Women’s Hospital, 75 Francis St., CWN-L1, Boston, MA 02115. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000076
104 cases-anesthesia-analgesia.org
a prominent leukocytosis with new thrombocytopenia. Review of the peripheral blood smear demonstrated immature monocytic forms consistent with leukemic blasts. Upon admission, the patient reported several days of night sweats, progressive fatigue, gingival bleeding, and diffuse bone and muscle pain. Laboratory evaluation revealed leukocytosis (39,000/μL), thrombocytopenia (59,000/μL), and normochromic macrocytic anemia (hemoglobin: 10.1 g/dL; mean corpuscular volume: 103.8 μm3). A peripheral smear revealed abundant monocytic forms in all stages of maturation with rare blast forms indicative of acute monocytic leukemia. The patient underwent an immediate bone marrow biopsy, and preliminary flow cytometry revealed AML with monocytic features. A multidisciplinary meeting with the patient, her family, and the relevant health care teams (obstetrics, obstetric anesthesia, and hematology/oncology) determined that urgent delivery would be necessary to enable the induction of chemotherapy. Initial discussions focused on a cesarean delivery performed under spinal anesthesia; however, this approach was ultimately abandoned due to the potential for introduction of malignant cells into the central nervous system (CNS) and resultant increased complexity of disease management. General anesthesia was therefore determined to be the safest option if a cesarean delivery was required. The patient indicated a strong preference to avoid cesarean delivery and general anesthesia, and thus labor was induced with oxytocin with an anticipated vaginal delivery. Intravenous analgesic drugs were discussed with the patient. Contingency planning included an emergent cesarean delivery performed under general anesthesia, with the intraoperative placement of an ultrasound-guided triplelumen central venous catheter for the postpartum initiation of chemotherapy. Labor analgesia was requested and achieved in the first stage of labor with IV patient-controlled analgesia using fentanyl (13 mcg bolus, 7-minute lockout, 300 mcg/4 h maximal dose, no basal infusion). During the second stage of labor, the patient experienced breakthrough pain and requested additional analgesia. Dexmedetomidine 50 mcg (0.5 mcg/kg) was administered IV over 10 minutes, with sufficient analgesic effect for the remainder of the second stage of labor; the patient did not require additional medication. She experienced no hypotension, bradycardia, or October 15, 2014 • Volume 3 • Number 8
oxyhemoglobin desaturation (continuous pulse oximetry remained 98%–99% with 4 L oxygen face mask). Ninety minutes later, a healthy male neonate was delivered with 1- and 5-minute Apgar scores of 9 and 9, respectively.
DISCUSSION
Acute leukemia, either myeloid or lymphoid, is one of the most common malignancies to occur in pregnancy and should be treated immediately to optimize maternal prognosis.2 When diagnosed in the first trimester, patients are often advised to terminate the pregnancy due to the toxicity of chemotherapeutic drugs and the frequent need for stem cell transplantation.1 In the second and third trimesters, chemotherapy is often initiated because the risk of teratogenicity is decreased,3 but the timing of delivery and post-chemotherapeutic pancytopenia remain of concern. Importantly, the neurodevelopmental outcomes of children with intrauterine chemotherapy exposure appear no different than that of the general population.4,5 However, when the age of the fetus is closer to term, minimizing fetal chemotherapy exposure by early delivery is accepted as a prudent management strategy. The anesthetic management of a patient with chronic neutrophilic leukemia during pregnancy was recently reported,6 but to our knowledge the peripartum management of a patient with acute leukemia has not been described. While both acute and chronic leukemia may predispose patients to both hemorrhage and thrombosis,7 due to thrombocytopenia and the presence of malignancy, respectively, chronic leukemia does not typically present with thrombocytopenia until later stages.8 Thus, acute leukemia is more likely to present an unpredictable bleeding risk. Whether the presence of concurrent AML and pregnancy, itself a hypercoagulable state,9 increases the risk of venous thromboembolism has not been reported. However, other myelodysplastic conditions, such as essential thrombocytosis and polycythemia vera, present an increased risk for venous and arterial thrombosis with pregnancy.10 Patients with acute leukemia, or blast crisis phase of chronic leukemia, often present with severe thrombocytopenia, which enhances the risk for postpartum hemorrhage and increases the risk for epidural hematoma with neuraxial techniques. While there are no strict guidelines regarding a minimal platelet count necessary for a neuraxial technique, anesthesiologists often avoid neuraxial techniques in patients with platelet counts 10 red blood cells per microliter, had worse event-free survival than their counterparts
October 15, 2014 • Volume 3 • Number 8
without CNS disease. While the reasons for these worse outcomes are unclear, several groups have attributed the increased mortality to the introduction of hematogenously circulating blast cells into the cerebrospinal fluid at the time of lumbar puncture.11–14 Thus, while the risk of spinal anesthesia in the patient with untreated AML is unknown, these studies would suggest that resultant worsening of oncologic outcome is possible. Although the epidural technique per se should not increase this risk, inadvertent dural puncture occurs in approximately 0.19% to 3.6% of epidural techniques in laboring women.15 Due to these considerations, and in consultation with our obstetric and hematologic colleagues, we decided to manage labor analgesia with an IV fentanyl patient-controlled analgesia with dexmedetomidine for breakthrough pain relief. Although dexmedetomidine has received only limited clinical evaluation during pregnancy, when compared with clonidine, it has an 8-fold greater α-2 selectivity,16 less fetal transfer in an in vitro placental model,17 and minimal, if any, effects on fetal physiology during labor.18 Dexmedetomidine may also offer several benefits to obstetric patients. First, animal studies have demonstrated analgesic synergism between fentanyl and α-2 agonists.19 Additionally, while opioids and local anesthetics may decrease the effectiveness of in vitro uterine contractions,20 α-2 agonists have been observed in in vitro studies to increase the frequency and amplitude of human myometrial contractions.21 Although not currently approved for use during pregnancy, dexmedetomidine has been used successfully in parturients for labor analgesia,22 general anesthesia for cesarean delivery,22 and nonobstetric surgery.23
CONCLUSIONS
Our case illustrates the importance of a multidisciplinary approach to the pregnant patient with a newly diagnosed acute hematologic malignancy. While AML in pregnancy is rare, the risks of inadvertent CNS seeding and subsequent prognostic implications are relative contraindications to the performance of neuraxial techniques. E REFERENCES 1. Brenner B, Avivi I, Lishner M. Haematological cancers in pregnancy. Lancet 2012;379:580–7 2. Chelghoum Y, Vey N, Raffoux E, Huguet F, Pigneux A, Witz B, Pautas C, de Botton S, Guyotat D, Lioure B, Fegueux N, Garban F, Saad H, Thomas X. Acute leukemia during pregnancy: a report on 37 patients and a review of the literature. Cancer 2005;104:110–7 3. Selig BP, Furr JR, Huey RW, Moran C, Alluri VN, Medders GR, Mumm CD, Hallford HG, Mulvihill JJ. Cancer chemotherapeutic agents as human teratogens. Birth Defects Res A Clin Mol Teratol 2012;94:626–50 4. Avilés A, Neri N. Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. Clin Lymphoma 2001;2:173–7 5. Nulman I, Laslo D, Fried S, Uleryk E, Lishner M, Koren G. Neurodevelopment of children exposed in utero to treatment of maternal malignancy. Br J Cancer 2001;85:1611–8 6. Taylor J, Roboz GJ, Baergen RN, Genc MR. Pregnancy in a woman with chronic neutrophilic leukemia. Obstet Gynecol 2013;121:457–60 7. Kwaan HC. Double hazard of thrombophilia and bleeding in leukemia. Hematology Am Soc Hematol Educ Program 2007:151–7 8. Enright H, Bond J. Chronic leukemias. Dis Mon 2008;54:242–55 9. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003;16:153–68
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10. Barbui T, Finazzi G. Myeloproliferative disease in pregnancy and other management issues. Hematology Am Soc Hematol Educ Program 2006:246–52 11. Gajjar A, Harrison PL, Sandlund JT, Rivera GK, Ribeiro RC, Rubnitz JE, Razzouk B, Relling MV, Evans WE, Boyett JM, Pui CH. Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia. Blood 2000;96:3381–4 12. Bürger B, Zimmermann M, Mann G, Kühl J, Löning L, Riehm H, Reiter A, Schrappe M. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003;21:184–8 13. te Loo DM, Kamps WA, van der Does-van den Berg A, van Wering ER, de Graaf SS. Prognostic significance of blasts in the cerebrospinal fluid without pleiocytosis or a traumatic lumbar puncture in children with acute lymphoblastic leukemia: experience of the Dutch Childhood Oncology Group. J Clin Oncol 2006;24:2332–6 14. Kebelmann-Betzing C, Seeger K, Wolf R, Henze G. Traumatic lumbar puncture at diagnosis and outcome in childhood acute lymphoblastic leukemia. Blood 2001;98:3496–7 15. Heesen M, Klöhr S, Rossaint R, Van De Velde M, Straube S. Can the incidence of accidental dural puncture in laboring women be reduced? A systematic review and meta-analysis. Minerva Anestesiol 2013;79:1187–97 16. Coursin DB, Coursin DB, Maccioli GA. Dexmedetomidine. Curr Opin Crit Care 2001;7:221–6
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17. Ala-Kokko TI, Pienimäki P, Lampela E, Hollmén AI, Pelkonen O, Vähäkangas K. Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta. Acta Anaesthesiol Scand 1997;41:313–9 18. Uemura K, Shimazutsu K, McClaine RJ, McClaine DJ, Manson RJ, White WD, Benni PB, Reynolds JD. Maternal and preterm fetal sheep responses to dexmedetomidine. Int J Obstet Anesth 2012;21:339–47 19. Meert TF, De Kock M. Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats. Anesthesiology 1994;81:677–88 20. Nacitarhan C, Sadan G, Kayacan N, Ertugrul F, Arici G, Karsli B, Erman M. The effects of opioids, local anesthetics and adjuvants on isolated pregnant rat uterine muscles. Methods Find Exp Clin Pharmacol 2007;29:273–6 21. Sia AT, Kwek K, Yeo GS. The in vitro effects of clonidine and dexmedetomidine on human myometrium. Int J Obstet Anesth 2005;14:104–7 22. Palanisamy A, Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth 2009;18: 258–61 23. Souza KM, Anzoategui LC, Pedroso WC, Gemperli WA. [Dexmedetomidine in general anesthesia for surgical treatment of cerebral aneurysm in pregnant patient with specific hypertensive disease of pregnancy: case report.]. Rev Bras Anestesiol 2005;55:212–6
A & A case reports
