Anaesthesia, 1990, Volume 45, pages 722-725
Epidurography in premature infants
J. VAN NIEKERK, B. M. J. BAX-VERMEIRE, J. W. M. GEURTS
AND
P. P. G . KRAMER
Summary A caudal epidural catheter was inserted in 20 premature, high risk infants for abdominal or thoracic surgery under combined caudal epidural and general anaesthesia. Epidurography was used to conjirm the position of the catheter which was found to be misplaced in three patients. The catheter penetrated the dura in one case, in another the tip was located in an epidural vessel and in the third the catheter was seen to be curled up within the epidural space. It was concluded that epidurographic control is essential with this method of anaesthesia in very small infants, in whom it was found to provide considerable advantages despite serious risks.
Key words Anaesthesia; paediatric. Anaesthetic techniques; epidural, caudal.
Epidural anaesthesia with the use of a catheter is described for use in children.'" However, it seems to be employed seldom in premature infants, probably because of technical problems, which include those of access, and fear of the toxic effects of local anaesthetic drugs because of reduced plasma protein binding and prolonged elimination in the very young. A caudal single shot is the most frequently used regional technique for surgery below the level of the diaphragm in ~ h i l d r e n .A~ cranially directed catheter can be introduced via the sacral hiatus in infants to obtain analgesia for upper abdominal and thoracic surgery and can be left in place for postoperative pain relief.b Epidurography can be used to confirm the injection site and the position of the epidural catheter.&*
Patients and methods The trial was approved by the hospital ethics committee. Twenty premature infants scheduled for abdominal or thoracic surgery between October 1988 and June 1989 were studied. The surgical indications are listed in Table 1. All the infants were fasted for 3 hours before surgery. Premedication was with intramuscular atropine 0.01 mg/kg 30 minutes before induction of anaesthesia. Electrodes for the electrocardiograph and probes for plethysmography and pulse oximetry, and an automatic blood pressure cuff,
were attached on arrival in the operating room. General anaesthesia was induced with oxygen/room air and isoflurane (maximum 2%) (in order to avoid intestinal distension by nitrous oxide) using a facemask or tracheal tube previously inserted in the neonatal intensive care unit. An infusion of compound sodium lactate or glucose/saline was begun at a rate of 10 ml/kg/hour. Thereafter vecuronium 0.1 mg/kg was administered to facilitate tracheal intubation (if not already done) and mechanical ventilation of the lungs, by means of a Servo 900B ventilator, and anaesthesia was maintained with a mixture of oxygen/ compressed medical air and isoflurane 0.3%. End-tidal carbon dioxide was continuously monitored by a capnograph (Mijnhardt side-stream). Body temperature was recorded by an oesophageal probe. The infant was then placed in the lateral position. The skin over the sacral hiatus was punctured under sterile conditions with an 18-G intravenous needle before the caudal insertion of a 19-G Tuohy needle (Portex). The patient was tilted into a 20" head down position and after an aspiration test bupivacaine plain 0.25%, 1.25 ml/kg, was injected slowly into the caudal space. A 23-G catheter was directed cranially, through the Tuohy needle until the spinal cord segments to be blocked were reached, as indicated by the marks on the catheter. An X ray was taken using iohexol 300 mg/ml (Omnipaque 300, Nycomed) in normal saline (1:l) as contrast material (total volume 0.5 ml/kg), to check the position of the epidural catheter.
J. van Niekerk, MD, B.M.J. Bax-Vermeire, MD, J.W.M. Geurts MD, Institute of Anaesthesiology, P.P.G. Kramer, MD, Department of Pediatric Radiology, University Hospital for Children and Youth, 'Het Wilhelmina Kinderziekenhuis', PO Box 18009, 3501 CA, Utrecht, The Netherlands. Accepted 31 January 1990. 0003-2409/90/090722 + 04 %03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland
722
Epidurography in premature infants
Fig. 1. The arrow shows contrast in the epidural space (lateral view).
Fig. 2. The arrow indicates the lobulated appearance of the epidural space in the supine position.
Results The average age of the 20 infants was 10 days (range 0 to 60). They weighed an average of 1980 g (range 520 to 2750 gram). The various surgical conditions to be treated are listed in Table 1. All infants were described as poor risk. Eighteen premature infants received a single-bolus caudal block; the 23-G catheter passed easily in a cranial
Fig. 3. The arrow indicates a myelogram.
direction to the required level as determined by the markings on the catheter. There was a slight resistance to the passage of the catheter throughout its introduction. Two patients ( 5 and 11) for oesophageal surgery received 0.25% bupivacaine 1 ml/kg through the catheter without the bolus caudal injection. Analgesia was considered to be adequate in all the cases since the heart rate did not increase more than 10 beats per minute nor the blood
Table 1. Clinical data.
Patient number
Weight (g)
~~
Age (days)
Diagnosis
Postoperative mechanical ventilation
~~
1 2 3 4 5 6 7 8 9 10
11 12 13 14 15 16 17 18 19 20
1850 2300 2400 2000 2000 1970 2400 2650 2750 950 2000 1500 2000 2500 I900 2450 2500 520 2000 I100
60 7 14 14 1 1
21 1
7 I 1
14 14 24 7 7 3 3 4 2
723
Bilateral inguinal hernia Meconium ileus H ydronephrosis Annular pancreas Oesophageal atresia Duodenal atresia H ydronephrosis Volvulus Congenital megacolon Duodenal atresia Oesophageal atresia Meconium ileus Necrotising enterocolitis Necrotising enterocolitis Extrophiu vesicue Duodenal atresia Diaphragmatic hernia Hepatic haematoma Volvulus Hydronephrosis
-
+ + + + ++ + ++
724
J . van Niekerk et al.
Fig. 4. Visualisation of epidural vessels
(arrows).
Fig. 5. Arrow 1 shows nasogastric tube, Arrow 2 the curling up of the catheter at T,*.
pressure by more than 10 mmHg at the time of the incision, and the capnogram and plethysmogram were unchanged. Surgery lasted between 2 and 2.5 hours and no supplementary dosage of bupivacaine was required. A catheter was left in place in the 17 infants who had normal X ray findings. Pain relief was achieved for 48 hours with nicomorphine with an infusion pump. The catheter was removed in those infants with abnormal radiological findings and the surgical procedure was performed with the help of the bolus caudal block supplemented with general anaesthesia (case numbers 10, 11 and 16). There were 11 infants who needed mechanical ventilation of their lungs before operation and also after operation. This was because of surgical complications or poor respiratory function. The remaining nine infants’ tracheas were extubated at the end of the surgical procedure. Radiological jindings
An X ray was taken in the lateral position and displayed a typical strip of contrast in the spinal canal in seven cases. They confirmed that the tip of the catheter was in the epidural space (Fig. 1). The epidural contrast looked lobulated when the infant was in the supine position (Fig. 2). There were 10 patients in this group. The contrast is also seen to be unilateral. This occurs when the catheter is not in the midline and is due to the viscosity of the substance which delays the spread at first. No resistance at all was felt on introduction of the catheter in infant number 10. The X ray revealed a myelogram (Fig. 3) although cerebrospinal fluid was not obtained after repeated aspiration. This is probably a result of the small diameter of the catheter (0.63 mm). It was impossible to introduce the catheter further than 2. cm in infant number 12. We were unable to aspirate blood even though
Fig. 6. The arrow indicates epidural contrast (0.125 ml ioxhexol 300+ 0.125 ml saline) in a 520-g male.
the tip was located in an epidural vessel (Fig. 4). The resistance while introducing the catheter was greater than normal in one case, number 16, and the catheter was seen to be curled up in the epidural space (Fig. 5). Figure 6 shows that an epidural catheter can be inserted in an infant weighing as little as 520 grams.’
Discussion Premature infants who have surgery display marked increases in heart rate and blood pressure.g.’OHormonal studies in this age group show an increase in blood levels of stress hormones, during and after operation comparable with, or in excess of, those found in adults, under different types of general anaesthesia.” Surgical stress results in a postoperative catabolic response which can be both prolonged and considerable.Il Furthermore, psychological sequelae of neonatal pain are postulated. Pain after operations might be expected to exacerbate these undesirable effects. Booker’*states that a recent survey showed that 48% of anaesthetists fail to provide any form of analgesia after major surgery in neonates. The reasons for this are probably historical: the discredited idea that neonates do not feel pain and the fear of respiratory depression resulting from the use of narcotic analgesics. Recent work has rendered such an approach untenable and indicates that the increasing use of regional anaesthesia in paediatrics’) should extend to the preterm neonate. Another factor of great importance is the iatrogenic morbidity associated with mechanical ventilation of the lungs in the premature infant.I4 Eleven patients in our series were already receiving mechanical ventilation of the lungs before surgery, but the remaining nine infants were on the verge of respiratory failure and would have undoubtedly
Epidurography in premature infants required ventilation after operation if a regional technique were not used. Single shot caudal or spinal anaesthesia are the only other forms of regional block applicable in these tiny patients. The duration of the block cannot be extended with either method longer than that achieved by the addition of adrenaline, and prolonged postoperative analgesia is not provided. Single shot caudal anaesthesia does not extend high enough for operations above the diaphragm. We injected bupivacaine via the epidural catheter to obtain thoracic anaesthesia in two cases and used this catheter to obtain postoperative analgesia in 17 patients. We used a single caudal shot of bupivacaine for subdiaphragmatic operations, but injection through the catheter would have reduced the volume of drug required. We intend to use the latter method in all cases. None of our patients required a supplementary dose of bupivacaine, but the majority of operations were of a duration close to that of the maximal duration of action of bupivacaine. We consider misplacement of the catheter in 15% of our 20 patients to be too high. Bosenberg6 used a caudal epidural catheter for biliary surgery in 20 infants and only one failed to reach the required spinal segment. However, his smallest infant was equal in weight to the largest in our series. The authors have considerable experience in the insertion of caudal epidural catheters in full term neonates and infants but this series is a report of the results with their first 20 preterm neonates. It was expected that experience would lead to a higher success rate and since this article was written we have used a caudal epidural catheter correctly in a further 10 similar infants. The advantages of the technique are clear. Our aim in this report. of our very first series, is to indicate the difficulties we encountered and the experience required in the insertion of caudal epidural catheters. Serious complications can be avoided by identification of misplacement by means of epidurography.
725
Acknowledgment We thank Miss S. Rijken for secretarial assistance.
References 1. RUSTONFG. Epidural anaesthesia in infants and children. Canadian Anaesthetists’ Society Journal 1954; I: 3 7 4 . LA, JEDEIKIN RJ, SHALEV D, HOFFMAN S. Epidural 2. SHAPIRO morphine analgesia in children. Anesthesiology 1984; 61: 2 10-2. C, DUBOUSSET AM, SAMIIK. Lumbar and thoracic 3. ECOFFEY
epidural anesthesia for urologic and upper abdominal surgery infants and children. Anesthesiology 1986; 6 5 87-90. P, FRANZA. Thoracale periduralanaesthesie in 4. HOFFMANN Kindesalter. Regional-Anaesthesie 1989; 1 2 25-9. (English title: Thoracic peridural anaesthesia in childhood.) LM, HANALLAH RS, NORDONJM, MCGILLWA. 5. BROADMAN ‘Kiddie caudals’: experience with 1 154 consecutive cases without complications. Anesthesia and Analgesia 1987; 66: S 18. 6. B~SENBERG AT, BLAND BAR, SCHULTE-STEINBERG 0, DOWNING JW. Thoracic epidural anesthesia via caudal route in infants. Anesthesiology 1989: 6 9 265-9. 7. SLAPPENDELR, GIELEN MJM, HASENBOS MAWM, HEYSTRATEN FMJ. Spread of radiopaque dye in the thoracic epidural space. Anaesthesia 1988; 4 3 93942. 8. MEHTAM, SALMON N. Extradural block. Confirmation of the injection site by X-ray monitoring. Anuesthesia 1985; 4 0 1009- 12. 9. WILLIAMSON PS, WILLIAMSON ML. Physiologic stress reduction by a local anesthetic drug newborn circumcision. Pediatrics 1983; 71: 3 W O . BJ, GOVERNMAN HD, KLAUBER MR, 10. HOLVERL, BROMBERGER DIXONSD, SNYDER JM. Regional anesthesia during newborn circumcision. Effect on infant pain response. Cfinical Pediatrics 1983; 22: 813-8. 11. ANANDKJS, HICHEYPR. Pain and its effects in the human neonate and fetus. New England Journal of Medicine 1987; 317: 1321-9. PD. Postoperative analgesia for neonates. Anaesthesia 12. BOOKER 1987; 42: 3434. 13. DALENSB. Regional anesthesia in children. Anesthesia and Analgesia 1989; 68:654-72. R. Reducing iatrogenic lung disease in the 14. PERELMAN premature newborn. Seminars in Perinatology 1986; 1 0 217-23.
Epidurography in premature infants
J. VAN NIEKERK, B. M. J. BAX-VERMEIRE, J. W. M. GEURTS
AND
P. P. G . KRAMER
Summary A caudal epidural catheter was inserted in 20 premature, high risk infants for abdominal or thoracic surgery under combined caudal epidural and general anaesthesia. Epidurography was used to conjirm the position of the catheter which was found to be misplaced in three patients. The catheter penetrated the dura in one case, in another the tip was located in an epidural vessel and in the third the catheter was seen to be curled up within the epidural space. It was concluded that epidurographic control is essential with this method of anaesthesia in very small infants, in whom it was found to provide considerable advantages despite serious risks.
Key words Anaesthesia; paediatric. Anaesthetic techniques; epidural, caudal.
Epidural anaesthesia with the use of a catheter is described for use in children.'" However, it seems to be employed seldom in premature infants, probably because of technical problems, which include those of access, and fear of the toxic effects of local anaesthetic drugs because of reduced plasma protein binding and prolonged elimination in the very young. A caudal single shot is the most frequently used regional technique for surgery below the level of the diaphragm in ~ h i l d r e n .A~ cranially directed catheter can be introduced via the sacral hiatus in infants to obtain analgesia for upper abdominal and thoracic surgery and can be left in place for postoperative pain relief.b Epidurography can be used to confirm the injection site and the position of the epidural catheter.&*
Patients and methods The trial was approved by the hospital ethics committee. Twenty premature infants scheduled for abdominal or thoracic surgery between October 1988 and June 1989 were studied. The surgical indications are listed in Table 1. All the infants were fasted for 3 hours before surgery. Premedication was with intramuscular atropine 0.01 mg/kg 30 minutes before induction of anaesthesia. Electrodes for the electrocardiograph and probes for plethysmography and pulse oximetry, and an automatic blood pressure cuff,
were attached on arrival in the operating room. General anaesthesia was induced with oxygen/room air and isoflurane (maximum 2%) (in order to avoid intestinal distension by nitrous oxide) using a facemask or tracheal tube previously inserted in the neonatal intensive care unit. An infusion of compound sodium lactate or glucose/saline was begun at a rate of 10 ml/kg/hour. Thereafter vecuronium 0.1 mg/kg was administered to facilitate tracheal intubation (if not already done) and mechanical ventilation of the lungs, by means of a Servo 900B ventilator, and anaesthesia was maintained with a mixture of oxygen/ compressed medical air and isoflurane 0.3%. End-tidal carbon dioxide was continuously monitored by a capnograph (Mijnhardt side-stream). Body temperature was recorded by an oesophageal probe. The infant was then placed in the lateral position. The skin over the sacral hiatus was punctured under sterile conditions with an 18-G intravenous needle before the caudal insertion of a 19-G Tuohy needle (Portex). The patient was tilted into a 20" head down position and after an aspiration test bupivacaine plain 0.25%, 1.25 ml/kg, was injected slowly into the caudal space. A 23-G catheter was directed cranially, through the Tuohy needle until the spinal cord segments to be blocked were reached, as indicated by the marks on the catheter. An X ray was taken using iohexol 300 mg/ml (Omnipaque 300, Nycomed) in normal saline (1:l) as contrast material (total volume 0.5 ml/kg), to check the position of the epidural catheter.
J. van Niekerk, MD, B.M.J. Bax-Vermeire, MD, J.W.M. Geurts MD, Institute of Anaesthesiology, P.P.G. Kramer, MD, Department of Pediatric Radiology, University Hospital for Children and Youth, 'Het Wilhelmina Kinderziekenhuis', PO Box 18009, 3501 CA, Utrecht, The Netherlands. Accepted 31 January 1990. 0003-2409/90/090722 + 04 %03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland
722
Epidurography in premature infants
Fig. 1. The arrow shows contrast in the epidural space (lateral view).
Fig. 2. The arrow indicates the lobulated appearance of the epidural space in the supine position.
Results The average age of the 20 infants was 10 days (range 0 to 60). They weighed an average of 1980 g (range 520 to 2750 gram). The various surgical conditions to be treated are listed in Table 1. All infants were described as poor risk. Eighteen premature infants received a single-bolus caudal block; the 23-G catheter passed easily in a cranial
Fig. 3. The arrow indicates a myelogram.
direction to the required level as determined by the markings on the catheter. There was a slight resistance to the passage of the catheter throughout its introduction. Two patients ( 5 and 11) for oesophageal surgery received 0.25% bupivacaine 1 ml/kg through the catheter without the bolus caudal injection. Analgesia was considered to be adequate in all the cases since the heart rate did not increase more than 10 beats per minute nor the blood
Table 1. Clinical data.
Patient number
Weight (g)
~~
Age (days)
Diagnosis
Postoperative mechanical ventilation
~~
1 2 3 4 5 6 7 8 9 10
11 12 13 14 15 16 17 18 19 20
1850 2300 2400 2000 2000 1970 2400 2650 2750 950 2000 1500 2000 2500 I900 2450 2500 520 2000 I100
60 7 14 14 1 1
21 1
7 I 1
14 14 24 7 7 3 3 4 2
723
Bilateral inguinal hernia Meconium ileus H ydronephrosis Annular pancreas Oesophageal atresia Duodenal atresia H ydronephrosis Volvulus Congenital megacolon Duodenal atresia Oesophageal atresia Meconium ileus Necrotising enterocolitis Necrotising enterocolitis Extrophiu vesicue Duodenal atresia Diaphragmatic hernia Hepatic haematoma Volvulus Hydronephrosis
-
+ + + + ++ + ++
724
J . van Niekerk et al.
Fig. 4. Visualisation of epidural vessels
(arrows).
Fig. 5. Arrow 1 shows nasogastric tube, Arrow 2 the curling up of the catheter at T,*.
pressure by more than 10 mmHg at the time of the incision, and the capnogram and plethysmogram were unchanged. Surgery lasted between 2 and 2.5 hours and no supplementary dosage of bupivacaine was required. A catheter was left in place in the 17 infants who had normal X ray findings. Pain relief was achieved for 48 hours with nicomorphine with an infusion pump. The catheter was removed in those infants with abnormal radiological findings and the surgical procedure was performed with the help of the bolus caudal block supplemented with general anaesthesia (case numbers 10, 11 and 16). There were 11 infants who needed mechanical ventilation of their lungs before operation and also after operation. This was because of surgical complications or poor respiratory function. The remaining nine infants’ tracheas were extubated at the end of the surgical procedure. Radiological jindings
An X ray was taken in the lateral position and displayed a typical strip of contrast in the spinal canal in seven cases. They confirmed that the tip of the catheter was in the epidural space (Fig. 1). The epidural contrast looked lobulated when the infant was in the supine position (Fig. 2). There were 10 patients in this group. The contrast is also seen to be unilateral. This occurs when the catheter is not in the midline and is due to the viscosity of the substance which delays the spread at first. No resistance at all was felt on introduction of the catheter in infant number 10. The X ray revealed a myelogram (Fig. 3) although cerebrospinal fluid was not obtained after repeated aspiration. This is probably a result of the small diameter of the catheter (0.63 mm). It was impossible to introduce the catheter further than 2. cm in infant number 12. We were unable to aspirate blood even though
Fig. 6. The arrow indicates epidural contrast (0.125 ml ioxhexol 300+ 0.125 ml saline) in a 520-g male.
the tip was located in an epidural vessel (Fig. 4). The resistance while introducing the catheter was greater than normal in one case, number 16, and the catheter was seen to be curled up in the epidural space (Fig. 5). Figure 6 shows that an epidural catheter can be inserted in an infant weighing as little as 520 grams.’
Discussion Premature infants who have surgery display marked increases in heart rate and blood pressure.g.’OHormonal studies in this age group show an increase in blood levels of stress hormones, during and after operation comparable with, or in excess of, those found in adults, under different types of general anaesthesia.” Surgical stress results in a postoperative catabolic response which can be both prolonged and considerable.Il Furthermore, psychological sequelae of neonatal pain are postulated. Pain after operations might be expected to exacerbate these undesirable effects. Booker’*states that a recent survey showed that 48% of anaesthetists fail to provide any form of analgesia after major surgery in neonates. The reasons for this are probably historical: the discredited idea that neonates do not feel pain and the fear of respiratory depression resulting from the use of narcotic analgesics. Recent work has rendered such an approach untenable and indicates that the increasing use of regional anaesthesia in paediatrics’) should extend to the preterm neonate. Another factor of great importance is the iatrogenic morbidity associated with mechanical ventilation of the lungs in the premature infant.I4 Eleven patients in our series were already receiving mechanical ventilation of the lungs before surgery, but the remaining nine infants were on the verge of respiratory failure and would have undoubtedly
Epidurography in premature infants required ventilation after operation if a regional technique were not used. Single shot caudal or spinal anaesthesia are the only other forms of regional block applicable in these tiny patients. The duration of the block cannot be extended with either method longer than that achieved by the addition of adrenaline, and prolonged postoperative analgesia is not provided. Single shot caudal anaesthesia does not extend high enough for operations above the diaphragm. We injected bupivacaine via the epidural catheter to obtain thoracic anaesthesia in two cases and used this catheter to obtain postoperative analgesia in 17 patients. We used a single caudal shot of bupivacaine for subdiaphragmatic operations, but injection through the catheter would have reduced the volume of drug required. We intend to use the latter method in all cases. None of our patients required a supplementary dose of bupivacaine, but the majority of operations were of a duration close to that of the maximal duration of action of bupivacaine. We consider misplacement of the catheter in 15% of our 20 patients to be too high. Bosenberg6 used a caudal epidural catheter for biliary surgery in 20 infants and only one failed to reach the required spinal segment. However, his smallest infant was equal in weight to the largest in our series. The authors have considerable experience in the insertion of caudal epidural catheters in full term neonates and infants but this series is a report of the results with their first 20 preterm neonates. It was expected that experience would lead to a higher success rate and since this article was written we have used a caudal epidural catheter correctly in a further 10 similar infants. The advantages of the technique are clear. Our aim in this report. of our very first series, is to indicate the difficulties we encountered and the experience required in the insertion of caudal epidural catheters. Serious complications can be avoided by identification of misplacement by means of epidurography.
725
Acknowledgment We thank Miss S. Rijken for secretarial assistance.
References 1. RUSTONFG. Epidural anaesthesia in infants and children. Canadian Anaesthetists’ Society Journal 1954; I: 3 7 4 . LA, JEDEIKIN RJ, SHALEV D, HOFFMAN S. Epidural 2. SHAPIRO morphine analgesia in children. Anesthesiology 1984; 61: 2 10-2. C, DUBOUSSET AM, SAMIIK. Lumbar and thoracic 3. ECOFFEY
epidural anesthesia for urologic and upper abdominal surgery infants and children. Anesthesiology 1986; 6 5 87-90. P, FRANZA. Thoracale periduralanaesthesie in 4. HOFFMANN Kindesalter. Regional-Anaesthesie 1989; 1 2 25-9. (English title: Thoracic peridural anaesthesia in childhood.) LM, HANALLAH RS, NORDONJM, MCGILLWA. 5. BROADMAN ‘Kiddie caudals’: experience with 1 154 consecutive cases without complications. Anesthesia and Analgesia 1987; 66: S 18. 6. B~SENBERG AT, BLAND BAR, SCHULTE-STEINBERG 0, DOWNING JW. Thoracic epidural anesthesia via caudal route in infants. Anesthesiology 1989: 6 9 265-9. 7. SLAPPENDELR, GIELEN MJM, HASENBOS MAWM, HEYSTRATEN FMJ. Spread of radiopaque dye in the thoracic epidural space. Anaesthesia 1988; 4 3 93942. 8. MEHTAM, SALMON N. Extradural block. Confirmation of the injection site by X-ray monitoring. Anuesthesia 1985; 4 0 1009- 12. 9. WILLIAMSON PS, WILLIAMSON ML. Physiologic stress reduction by a local anesthetic drug newborn circumcision. Pediatrics 1983; 71: 3 W O . BJ, GOVERNMAN HD, KLAUBER MR, 10. HOLVERL, BROMBERGER DIXONSD, SNYDER JM. Regional anesthesia during newborn circumcision. Effect on infant pain response. Cfinical Pediatrics 1983; 22: 813-8. 11. ANANDKJS, HICHEYPR. Pain and its effects in the human neonate and fetus. New England Journal of Medicine 1987; 317: 1321-9. PD. Postoperative analgesia for neonates. Anaesthesia 12. BOOKER 1987; 42: 3434. 13. DALENSB. Regional anesthesia in children. Anesthesia and Analgesia 1989; 68:654-72. R. Reducing iatrogenic lung disease in the 14. PERELMAN premature newborn. Seminars in Perinatology 1986; 1 0 217-23.
