Early extubation after cardiac surgery using combined intrathecal sufentanil and morphine

Early Extubation After Cardiac Surgery Using Combined Intrathecal Sufentanil and Morphine Jeffrey D. Swenson, MD, R. Michael Hullander, MD, Kenneth Wingler, MD, and David Leivers, FRCA The records of 10 patients who had well-preserved respiratory and ventricular function and had received 50 pg of sufentanil and 0.5 mg of morphine intrathecally before induction of anesthesia for cardiopulmonary bypass surgery were reviewed. Anesthesia was maintained with isoflurane and no patient received intravenous narcotics intraoperatively. Postoperative analgesic requirements were low, with 7 of 10 patients requiring no supplemental analgesic during the first 12 hours. Early extubation (within 8 hours of arrival in the intensive care unit) was possible in 8 patients; two patients remained intubated for reasons unrelated to the anesthetic

E

ARLY EXTUBATION has been advocated for patients undergoing cardiac surgery who have wellpreserved pulmonary and left ventricular function.1J Among the advantages cited by proponents of this view are reductions in respiratory complications, ventilatory support, and intensive care unit (ICU) requirements, as well as improved cardiac function and patient comfort. When early extubation is desired, techniques that have been used include combinations of inhalation agent with intravenous (IV) opioids3 or epidural local anesthetics.4 Current methods that include large doses of IV opioids result in sustained ventilatory depression due to prolonged systemic elimination.5p6Volatile anesthetics can facilitate early recovery but are associated with greater hemodynamic fluctuations7 and must be supplemented with other forms of analgesia early in the postoperative period. Epidural anesthesia produces sympathetic blockade and is associated with increased fluid requirements.4 Intrathecal (IT) opioids have been used widely, both intraoperatively as adjuvant anesthesia and postoperatively for analgesia.*-l3 Sufentanil, used intrathecally in doses as low as 10 pg, decreases volatile anesthetic requirements.14 Animal studies have shown that larger doses of IT opioids have progressively greater efficacy in diminishing the response to subsequent noxious stimuli.r5 The peak action of IT morphine occurs after 4 to 7 hour@ and therefore allows preoperative administration to produce maximal analgesia during the postoperative period. The intense intraoperative analgesia provided by IT sufentanil, along with the postoperative analgesia provided by IT morphine, make the combination a suitable choice for cardiac surgery. Varying amounts of IT sufentanil and morphine have been used as adjuvants to volatile anesthetics for cardiac surgery at this institution. A standardized technique has been used in patients for whom early extubation was planned. Patients having significant pulmonary disease, repeat sternotomies, ventricular dysfunction, or coagulation disorders were not considered candidates for this technique. The surgeons and ICU staff were educated to the potential offered by this technique for earlier recovery compared to commonly used IV opioid anesthetics. From manual intraoperative anesthesia records and computerized ICU archives, details of 10 consecutive patients who had received a standard dose of IT sufentanil and morphine for cardiac surgery without additional intraopera-

technique. No patient required naloxone, reintubation, or treatment for respiratory depression. Combined intrathecal sufentanil and morphine provided conditions that allowed successful early extubation in 8 of 10 of these selected cardiac surgery patients. This is a US government work. There are no restrictions on its use. KEY WORDS: cardiac surgery, extubation, tanif, morphine, anesthetic technique.

intrathecal,

sufen-

tive opioids were obtained. The findings and results from this series of patients are reported. METHODS

After obtaining Institutional Review Board approval for retrospective examination, the records of 10 consecutive patients with normal left ventricular function undergoing cardiac surgery were reviewed. All patients had been considered suitable for early extubation and had received the standard perioperative management. Preoperative medications, including calcium channel blockers, B-blockers, and nitrates, were continued until the induction of anesthesia. Two hours prior to induction of anesthesia, each patient received morphine, 0.1 mg/kg, and scopolamine, 5 p,g/kg, intramuscularly, which provided sedation for the establishment of arterial and venous access. A lumbar puncture was performed in the lateral decubitus position using a 25-gauge Quincke-tipped needle and undiluted sufentanil, 0.005%, 1 mL (50 kg), and preservative-free morphine, 0.05%, 1 mL (0.5 mg) were injected into the intrathecal space. A central venous or pulmonary artery catheter was inserted immediately before induction of anesthesia. After preoxygenation, anesthesia was induced by titrating midazolam (up to 0.1 mg/kg IV) until loss of consciousness. The patient was then ventilated by mask, and vecuronium bromide, 0.15 mg/kg, was used to facilitate endotracheal intubation. Esmolol was administered as needed to diminish the hemodynamic response to intubation. No additional vasoactive agents or P-blockers were required between intubation and institution of cardiopulmonary bypass (CPB). Inhalation anesthesia was maintained with air, oxygen, and isoflurane. The end-tidal concentration of isoflurane was measured by mass spectrometry (PPG Biomedical Systems, Lenexa, KA) and recorded at 5-minute intervals. Muscle relaxation

From the Departments ofAnesthesiology and Clinical Investigation, Naval Hospital, San Diego, CA. Sponsored by the Chief Navy Bureau of Medicine and Surgery, Washington, DC, Clinical Investigation Program, No. S-94-001. This paper was presented in part at the Anesthesia Update 1994 Meeting, University of Wisconsin, at Copper Mountain, CO, February 8, 1994. The views expressed m this article are those of the authors and do not reflect the oficial policy or position of the Department of the Navy, Depattment of Defense, or the United States Government. Address reprint requests to LCDR J.D. Swenson, MD, USNR, c/o Clinical Investigation Department, Naval Medical Center, San Diego, CA 92134-5000. This is a USgovernment work. There are no restrictions on its use. 1053-0770/94/0805-0005$00.00/0

Journalof Cardiothoracicand VascularAnesthesia, Vol8, No 5 (October), 1994: pp 509-514

509

SWENSON

510

was maintained

by supplemental doses of vecuronium, 0.07 mgikg IV. was given immediately before

Table 2. Operative Details for Patients Receiving

and mid-

bypass and again during rewarming to prevent awareness. After initiation of CPB the patients were cooled to 28°C. After separation from azolam,

bypass, patients were treated with sodium nitroprusside and/or dopamine to maintain a cardiac index greater than 2.5 L/minim’ and/or a systolic pressure of 100 to 120 mmHg. Anesthesia after CPB was maintained with isoflurane without IV opioids. Following surgery, a standard cardiac protocol was used including mechanical ventilation to maintain normocarbia and treatment of pain with morphine, 1.0-5.0 mg/h IV. Sodium nitroprusside was given by infusion to treat hypertension. After ensuring normothermia, neostigmine, 0.05 mgikg, and glycopyrrolate, 0.01 mgikg IV, were given as needed to reverse residual neuromuscular blockade. The ICU staff frequently assessed the level of patient awareness and comfort, and the earliest appropriate response to verbal commands was recorded in the computerized nursing notes. The criteria established for tracheal extubation were (1) hemodynamic stability without inotropic support, (2) minimal chest tube drainage, and (3) spontaneous ventilation for 30 minutes with a PaC02 < SO mmHg, pH greater than 7.30, and Pa02 greater than 75 mmHg on an F102 less than 0.40. Following extubation, arterial blood gas values on 50% oxygen via face mask were measured after 30 minutes. Analgesia was maintained with IV morphine as required. The manually recorded anesthesia record was used to obtain hemodynamic data, dosage and timing of anesthetic agents, and CPB details in the operative period. The time to extubation, analgesic requirements, vasoactive drug dosage, and any complications were derived from the computerized ICU nursing record that had been compiled during the postoperative period. Numerical values are expressed as means + SEM. RESULTS

The demographic data for patients described in this series are shown in Table 1. Operative details, including the type of procedure performed, duration of bypass, and aortic cross-clamp time are recorded in Table 2. Eight patients had coronary artery bypass graft surgery, whereas one patient underwent tricuspid valve replacement and one had repair of atria1 and ventricular septal defects. All lumbar punctures were performed in a holding area adjacent to the operating room without reported difficulty. No patient became unresponsive before induction of anesthesia in the operating room. The mean time between lumbar puncture and intubation was 18 minutes (range 9-33 minutes). Esmolol was required in 8 of 10 patients to blunt

lntrathecal Sufentanil ___.

_____-

CPB Patient

Time

Procedure

Aortic

(min)

Cross-Clamp

Time

(mm)

1

CABG

48

33

2

CABG

75

45

3

CABG

104

56

4

ASDIVSD

60

30

5

CABG

57

48

6

CABG

76

46

7

CABG

32

15

8

CABG

79

50

CABG

113

57

92

70

9 10

NR

73 2 8

45 + 5

NOTE. Values expressed as Mean -c SEM. Abbreviations:

CABG, coronary artery bypass graft; TVR, tricuspid

valve replacement; ASD, atrial septal defect; VSD, ventricular septal defect.

only the hemodynamic response to intubation. The systolic pressure and heart rate remained stable between induction and initiation of CPB (Figs 1 and 2). The end-tidal isoflurane concentration required to maintain stability fluctuated minimally (0.4%-0.6%) during sternotomy, mediastinal dissection, and cannulation of the great vessels (Fig 3). No patient received IV narcotic during anesthesia (Table 3). The bypass period was uneventful for all patients, and there were no intraoperative surgical complications that would have necessitated delaying extubation. Upon separation from bypass, 2 of 10 patients received less than 5.0 kglkglmin of dopamine, and 4 of 10 received sodium nitroprusside, 051.0 p,g/kg/min, to maintain systolic blood pressure within the prescribed limits. Times from arrival in the ICU to awakening and to extubation were 1.3 ” 0.2 hours and 6.3 +- 1.4 hours, respectively (Table 4). Eight patients were extubated within 8 hours of arrival in the ICU (Fig 4). Two patients remained intubated and ventilated

150k 130 G I E

Table 1. Demographic Data

ET Ai

-

llO-

E Patient

Age

(yrsl

Sex

Height

(cm)

Weight

(kg) 0

1

63

M

183

90

2

56

M

182

79

3

61

M

185

80

4

43

F

152

62

5

47

M

175

70

6

40

M

173

103

7

69

M

170

90

8

61

M

165

75

9

42

M

177

98

10

28

F

160

62

51 t4

8M/2F

174&3

NOTE. Values expressed as Mean 5 SEM.

81 -f 5

go

-

70

-

2

50

. I

.

. 10

.

. 20

.

Tune N=

10

10

10

. 30

.

After

lntubation

10

. 40

10

.

. 50

.

. 60

.

. 70

.

. 60

.

, 90

(minutes) 10

10

6

4

1

Fig 1. The systolic blood pressure (SBP) recorded at B-minute intervals from the time of intubation (I) until initiation of CPB. The number of patients IN) approaches 0 as succaesive patients are placed on CPB. Data are preaentad ae mean * SEM.

INTRATHECAL SUFENTANIL FOR CARDIAC SURGERY

511

Table 3. Total Intravenous Narcotic (morphine oulphate, mg) Administered lntraoperatively

and During 12 and 24 Hours

After lntrathecal Injection Patient

Narcotics

12

Hours

24 Hours 20 2 0 0 10 1 0 10

0

.

I

.

.

.

10

20

10

10

N=lO Fig 2. time of patients Data are

.

.

.

.

.

.

.

.

.

.

.

30 40 50 60 Tima After lntubation (minutes) 10

10

10

10

.

.

.

9

.

70

60

90

8

4

1

10

The heart rate (HR) recorded at 5-minute intervals from the intubation (I) until the initiation of CPB. The number of (N) approaches 0 as successive patients are placed on CPB. presented as mean f SEM.

more than 8 hours for treatment of an increased alveolar-toarterial oxygen gradient and persistent hypotension. These patients were subsequently extubated without further incident. Arterial blood gas measurements 30 minutes after extubation were satisfactory in all patients (Table 5). The mean PaC02 was 42.0 + 1.1 mmHg and the mean Pa02 (on 50% O2 via face mask) was 137.0 + 18.0 mmHg. No patient required reintubation or naloxone for respiratory depression. The mean IV morphine requirement was 1.6 f 0.9 mg (range O-8) during the first 12 hours after the intrathecal injection, with 7 of 10 patients requiring no additional pain medication. The 24-hour supplemental morphine requirements were 8.2 * 3.1 mg (range O-29), with 3 of 10 patients still needing no analgesics (Table 3). The requirements for nitroprusside after arrival in the ICU are shown in Fig 5. The mean infusion rate of sodium nitroprusside (0.48 + 0.2

E

0

4

29

0

4

10

0

1.6 k 0.9

8.2 + 3.1

NOTE. Values expressed

as Mean

2 SEM.

ug/kg/min) was highest in the first hour and declined rapidly over the following 6 hours. DISCUSSION

Opioid-based anesthesia has been popular for patients undergoing cardiac surgery since the 1970s when studies demonstrated its ability to ensure hemodynamic stability in patients with marginal cardiac reserve.16J7 The beneficial cardiovascular effects of high-dose IV narcotic anesthesia are offset by the need to provide prolonged ventilatory support to manage the postoperative respiratory depression associated with this technique. The practice of continuing ventilatory support for up to 24 hours in patients undergoing cardiac surgery has been widely accepted.18,i9 Some anesthesiologists also advocate prolonged sedation and analgesia to decrease myocardial oxygen demand and reduce ischemia in the early postoperative period.20 Recently, however, the practice of prolonged sedation and ventilatory support has been more closely examined. Several author@ advocate early extubation (within 8 hours of arrival in the intensive care unit) for patients who meet acceptable preoperative, intraoperative, and postoperative criteria. If early extubation is anticipated, the anesthetic technique should provide conditions that allow stable intraoperative hemodynamics, rapid emergence, and early

3

2

.6-

7 ; z

Table 4. Time (hours) to Following Commands and Extubation

.

1

Patient

.4-

. .a -

0’.

. s

N= 10

.

10 10

.

.

.

.

1..

.

20 30 40 Time (minutes) After Sternotomy 10

10

10

50 a

.

.

.’

60 4

1

Fig 3. The percentage of end-tidal isoflurane recorded at B-minute intervals from stemotomy (S) until the initiation of CPB. The number of patients (N) approaches 0 as successive patients are placed on CPB. Data are expressed as mean f SEM.

Values

Following Commands

Extubation

1

1.1

4.7

2

1.5

5.5

3

1.5

3.5

4

0.3

2.0

5

1.5

5.3

6

2.0

17.5

7

0.7

9.9

8

1.6

4.2

9

1.5

7.5

10

2.0

3.0

1.3 f 0.2

6.3 ” 1.4

expressed

as Mean

? SEM.

SWENSON

123456789

10

11

12

Time (hours) After Arrivalin ICU Fig 4. The percentage of patients remaining intubated after arrival in the intensive care unit recorded at l-hour intervals.

restoration of spontaneous ventilation, yet still provide excellent postoperative analgesia. Both morphine and sufentanil are F-receptor agonists with activity at C-fiber terminals in the spinal cord. Recent studies suggest, however, that the efficacy of sufentanil is significantly greater than that of morphine.15**l,**The pharmacokinetics of sufentanil, as described by Hansdottir et a1,23 show a mean residence time of 0.92 hours in the intrathecal space with low plasma concentrations, making it a suitable agent when early restoration of spontaneous ventilation is desired. Higher dose IT sufentanil combined with IT morphine, therefore, was chosen to achieve potent intraoperative and postoperative analgesia, but still allow early extubation. Although not specifically questioned about side effects, patients appeared to tolerate the IT opioids well, with only mild complaints of pruritus postoperatively. The mean interval between lumbar puncture and anesthetic induction was 18 minutes (range 9-33 minutes) with all patients remaining responsive until given midazolam to produce unconsciousness. Esmolol was required in 8 of 10 patients during largngoscopy and intubation as the sufentanil did not reliably attenuate the hemodynamic response.

Table 5. Results of Arterial Blood Gas Samples 30 Minutes After Extubation With Patient Breathing 50% Oxygen by Face Mask Patient

PaO?(mmHg)

PaCOZ(mmHgl

PH

1

180

41

7.37

2

154

38

7.37

3

117

40

7.40

4

238

48

7.31

5

89

41

7.39

6

99

41

7.41

7

95

40

7.38

8

78

48

7.29

9

101

41

7.36

10

214

44

7.27

137 t- 18.0

42 2 1.1

7.36 lr 0.02

NOTE. Values expressed as Mean f SEM.

1

2

3 4 5 6 7 Time (hours)After ArrivalnnICU

8

9

El Ai.

10

Fig 5. The mean dose of nitroprusside (pg/kg/min) required for blood pressure control recorded at l-hour intervals after arrival in the intensive care unit. Data are expressed as mean f SEM.

However, during mediastinal dissection the mean end-tidal concentration of isoflurane (Fig 1) required to maintain the mean systolic arterial pressure at 100 to 130 mmHg was only 0.4% to 0.6%. IT opioids, therefore, appeared to reduce volatile anesthetic requirements during mediastinal dissection, but offered little benefit for tracheal intubation. The analgesic actions of IT opioids are at the C-fiber terminals of the substantia gelatinosa of the dorsal horn, but the pathways for nociception of bronchi and trachea are predominantly by A-fibers2” travelling in the vagus nerve to its brainstem nucleus. The mean time interval between lumbar injection of sufentanil and tracheal intubation was 18 minutes in these patients, which makes sufficient cephalad spread to the brainstem unlikely. There are no known spinal opioid receptors at the A-fiber terminals,2s and it is unknown whether opioids in the cerebrospinal fluid at the level of the vagal nucleus could significantly alter responses to noxious stimuli in the trachea. The mean heart rate during the period from intubation to initiation of CPB was 63.0 2 4.2 beatsimin and resembled the stability seen in cases using moderate to high-dose IV opioid anesthetic techniques.‘,i7 The bradycardia associated with IV opioids has been attributed to their action in the central vagal nucleus,26 and a similar mechanism may apply if large doses of sufentanil result in increasing concentrations near the brainstem after lumbar IT administration. The patients in this series were considered candidates for early extubation because they had well-preserved pulmonary and left ventricular function. The mean time from the patient arriving in the ICU to awakening and following commands was 1.3 2 0.2 hours, with time to extubation being 6.3 ? 1.4 hours. The interval from awakening to extubation likely reflects the concern by the surgeons to allow adequate time for complete rewarming, ensure adequate hemostasis, and overcome the period of maximal myocardial depression, which typically occurs 3 to 5 hours after separation from bypass.z7 Postoperatively, tracheal extubation was achieved in all

INTRATHECAL SUFENTANIL FOR CARDIAC SURGERY

513

but two patients within 8 hours. Neither of the patients who remained intubated had problems related to the IT opioids. The mean resting PaCOz of 42.0 + 1.1 mmHg and PaOz (on 50% 02 via face mask) of 137.0 f 18.0 mmHg 30 minutes after extubation show lack of excessive sedation and respiratory depression. Evidence of good analgesia is provided by the low mean IV morphine requirements. Seven patients required no additional analgesia, and the group mean dosage was only 1.6 2 0.9 mg during the first 12 hours postoperatively. This decreased IV narcotic demand is an expected result of prolonged analgesia from IT morphine. However, this effect may be augmented by the preemptive suppression of afferent transmission by IT opioids as described by Abram and Yaksh.28 They demonstrated a marked attenuation of response to subsequent noxious stimuli after prior administration of IT morphine. Other investigators have studied the effects of IT morphine in cardiac surgery patients with regard to hemodynamic stability, volatile anesthetic requirements, and postoperative analgesia.29,30 These patients, however, all received large doses of IV fentanyl or sufentanil intraoperatively, thus making it difficult to define any added effect of IT opioid. Additionally, those trials did not address using IT narcotics as a method of facilitating early extubation.

In this series, no patient received intraoperative IV opioids and postoperative analgesic requirements were low. These results, therefore, can be interpreted as more accurately reflecting the beneficial action of the intrathecal agents alone. Vanstrum et a129reported no neurologic complications in approximately 1,000 patients who received spinal opioids before cardiac surgery. There remains, however, a theoretical risk of a spinal or epidural hematoma after lumbar puncture in patients who will receive anticoagulants. All of these patients had normal preoperative coagulation function, and surgery would have been delayed in the event of a traumatic puncture. The combination of IT sufentanil and morphine provided stable intraoperative hemodynamics and allowed early extubation in the majority of these patients with good respiratory and ventricular function. It is believed that controlled prospective studies are needed to ascertain whether the technique of providing potent perioperative analgesia with this combination of opioids administered intrathecally does offer significant advantages over existing methods and to determine the optimal dose of IT sufentanil.

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