J Clin Monit Comput (2014) 28:319–323 DOI 10.1007/s10877-013-9523-9
BRIEF REPORT
The use of regional cerebral oximetry monitoring during controlled hypotension: a case series Brandon A. Van Noord • Christopher L. Stalker Peter Roffey • Duraiyah Thangathurai
•
Received: 28 March 2013 / Accepted: 12 October 2013 / Published online: 18 October 2013 Ó Springer Science+Business Media New York 2013
Abstract Regional cerebral oximetry monitoring was used to guide nitroglycerin infusion and IV fluid administration during controlled hypotension in order to optimize each individual patient’s mean arterial pressure in a series of 20 consecutive patients who underwent major open urological or abdominal surgery. Although controlled hypotension offers a definite benefit in patients undergoing complex surgery where blood loss will be elevated or would severely compromise the surgical field, it is not without risk as low arterial pressure may compromise tissue perfusion and promote ischemia. In this case series, despite an average mean arterial pressure decrease of 19.5 % (p \ 0.001), cerebral oximetry values increased by an average of 22.7 % (p \ 0.001) after the nitroglycerin infusion had been initiated (220 mcg/min average). Patients received an average of 3.15L crystalloid and 437 ml albumin in fluid resuscitation. Keywords Controlled hypotension Nitroglycerin Cerebral oximetry
1 Introduction Controlled hypotension has been shown to decrease blood loss, decrease transfusion rate, and improve visibility of the surgical field [1]. Electively lowering mean arterial B. A. Van Noord C. L. Stalker P. Roffey D. Thangathurai Department of Anesthesia, Keck Medical Center, University of Southern California, Los Angeles, CA, USA B. A. Van Noord (&) Department of Anesthesiology, LAC?USC Medical Center, 1200 N. State St., IPT, Room C4E100, Los Angeles, CA 90033, USA e-mail: [email protected]
pressure (MAP) is not without risk as it may potentially decrease regional cerebral blood flow [2]. Therefore, general recommendations to maintain cerebral auto-regulation include maintaining MAP [ 55 mmHg [3] and lowering MAP \ 30 % from baseline in hypertensive patients [4]. Unfortunately, commonly utilized physiological monitors do not detect tissue ischemia directly. At best, blood pressure (BP), heart rate (HR), and pulse oximetry (SpO2) indirectly measure tissue oxygenation. SpO2 measures peripheral arterial blood oxygen saturation, not tissue oxygen tension itself. It is unable to compare tissue oxygen demand relative to supply or determine microvascular blood flow. Serial arterial blood gas (ABG) monitoring can demonstrate anaerobic metabolism and suggest ischemia. However, serial ABG monitoring is suboptimal as it is expensive, invasive, contributes to blood loss, and does not provide continuous real-time information. Due to the fact that tissue perfusion is difficult to assess clinically, the optimal BP for an individual patient is difficult to surmise. Indeed, tissue hypoxia, cellular injury, and inflammatory mediator release may occur even in the presence of normal MAP, HR, and SpO2 [5]. Cerebral oximetry (rSO2) is a new modality that uses near-infrared spectroscopy to penetrate the skull and continually and non-invasively measure the cerebrovascular perfusion in the tissue lying directly underneath sensors applied to the forehead [6]. The single numerical value displayed combines venous (75 %) and arterial (25 %) blood volume saturations [7]. Validation studies have shown that rSO2 provides information on cerebral desaturation that is as accurate as information obtained invasively [8]. For example, during orthotopic liver transplantation, rSO2 desaturation correlated with biochemical markers of cerebral hypo-perfusion while hemodynamic variables did not [9].
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Clinically, rSO2 measurement allows the brain to be used as an index organ to assess global oxygenation and tissue perfusion. Theoretically, systemic benefits should be seen if cerebral deoxygenation is prevented during surgery. Recent prospective studies have shown this to be true. In patients undergoing CABG, maintaining cerebral oximetry greater than 75 % was associated with a lower incidence of postoperative ventilation [48 h, stroke, myocardial infarction, and repeat surgery [10]. In pediatric patients undergoing cardiopulmonary bypass to repair congenital cardiac anomalies, interventions based on rSO2 monitoring decreased postoperative neurological sequelae and length of stay [11]. While multiple agents may be used for controlled hypotension, nitroglycerin (NTG) is our agent of choice. NTG dilates venous capacitance vessels, has a short halflife, does not produce clinically toxic metabolites, and is not associated with a rebound phenomenon. As NTG may induce hypotension by increasing venous blood volume and reducing venous return, patients must be adequately volume resuscitated to maintain blood flow and prevent an adrenergic response [12].
2 Case series We report on 20 consecutive cases between January 12 and February 22, 2012. Institutional Review Board approval was obtained prior to case review. One-sample student’s t test was used to compare means [BMDP statistical software, version 8.1 (Statistical Solutions, Los Angeles, CA)]. Continuous variables are presented as mean ± standard deviation. A value of p B 0.05 was considered statistically significant. The same anesthetic team performed all cases and managed all patients post-operatively in the ICU. Anesthesia was induced with propofol, fentanyl, and ketamine and maintained with a low dose inhalational agent such as isoflurane in an air-oxygen mixture along with supplemental doses of ketamine and fentanyl. Depending on underlying renal function, muscle relaxation was produced with vecuronium or cisatricurium. In addition to standard ASA monitors, an arterial line was placed. NTG infusion, crystalloids, and colloids were titrated to maximize recorded rSO2. Baseline (pre-NTG) MAP, HR, rSO2, and FiO2 values were obtained prior to induction while the patient was breathing room air. The intra-op MAP, HR, rSO2, and FiO2 values were recorded during steady state anesthetic conditions. The FiO2 remained constant throughout the case with the only variable being the NTG infusion rate. The majority of patients were extubated prior to ICU transport. Post-operatively, the same intra-operative NTG dose was initially maintained. Patient demographics are presented in Table 1. The typical patient was an elderly male admitted for a radical
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cystectomy: 17 patients were male, the average age was 66, and 13 cases involved bladder excision for tumor. Patient 1 was a 26 year-old male Jehovah’s Witness who presented for excision of massive retroperitoneal metastases. He had previously received bleomycin for testicular cancer. Using rSO2 to guide NTG titration and fluid administration allowed for more aggressive decrease in blood pressure and resulted in an estimated intraoperative blood loss of only 300 ml. He was extubated at the end of the procedure and recovered uneventfully. Patient 16 was a 61 year-old male who underwent radical nephrectomy and caval thrombectomy. With the aid of the hypotensive technique described in this paper, blood loss was minimized to 200 ml and rSO2 increased 37 % during surgery. Hemodynamic changes, blood loss, and fluid management are presented in Tables 2 and 3. Mean hemodynamic changes are presented in Table 4 along with statistical significance. The average starting MAP was 90.3 ± 13.7 mmHg. After starting NTG, the average MAP decreased to 71.9 ± 14.3 mmHg intra-op. This represented an average decrease of 17.5 mmHg (19.5 %, p \ 0.0001) during surgery compared with baseline. Interestingly, the MAP actually increased in two patients after NTG initiation and adequate fluid resuscitation. The average starting HR was 74.3 ± 9.4 bpm. After starting NTG, the average
Table 1 Patient demographics #
Gender
Age
Procedure
1
M
26
RPLND and metastatic tumor excision
2
F
65
Robotic partial nephrectomy
3 4
F M
62 57
Radical cystectomy Radical cystectomy
5
M
81
Radical cystectomy
6
M
57
Radical cystectomy
7
M
33
B/L robotic partial nephrectomy
8
M
72
Radical cystectomy ? RPLND
9
M
80
Radical cystectomy
10
M
79
Radical cystectomy ? RPLND
11
M
86
Radical cystectomy ? RPLND
12
F
67
LAR for rectal cancer
13
M
72
Cystoprostatectomy, RPLND
14
M
67
Nephrouretectomy ? RPLND
15
M
84
Cystoprostatectomy, RPLND
16
M
61
Radical nephrectomy ? caval thrombectomy
17
M
64
Radical cystectomy ? RPLND
18
M
67
Radical cystectomy ? RPLND
19
M
70
Cystoprostatectomy, RPLND
20
M
66
Radical nephrectomy
RPLND retro-peritoneal lymph node dissection, LAR low abdominal resection
J Clin Monit Comput (2014) 28:319–323 Table 2 Hemodynamic changes
321
# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
MAP (mmHg)
HR (bpm)
rSO2 (L,R)
FiO2 (%)
NTG (mcg/min)
Baseline
73.3
86
77,78
21
Intra-op
56.3
64
77, 78
21
166
Baseline
78.7
75
76, 80
21
0
Intra-op
63
66
78, 85
100
Baseline
91
90
75, 74
21
0
333 0
Intra-op
56.7
76
88, 88
100
Baseline
80
70
78, 58
21
166
Intra-op
49.7
96
89, 68
56
333
Baseline
79
64
54, 57
21
0
Intra-op
74.7
78
69, 70
62
266 0
0
Baseline
89.3
81
54, 48
21
Intra-op
79.7
71
71, 69
50
233
Baseline
110.3
65
73, 68
21
0
Intra-op
55
69
84, 78
79
66
Baseline Intra-op
83 79.3
59 66
58, 60 78, 81
21 50
0 233 0
Baseline
92.3
62
59, 59
21
Intra-op
83.3
63
72, 73
60
333
Baseline
104.3
76
63, 63
21
0
Intra-op
87.3
84
80, 79
100
Baseline
68
65
65, 65
21
133 0
Intra-op
48
72
85, 83
100
Baseline
79.3
94
67, 64
21
249
Intra-op
69
88
67, 64
62
166.5
Baseline
101
76
77, 79
21
0
0
Intra-op
92.3
82
90, 95
75
166.5 0
Baseline
104.3
75
64, 60
21
Intra-op
83.7
78
79, 86
96
266
Baseline
98.3
69
55, 55
21
0
Intra-op
67.3
78
71, 69
97
133
Baseline Intra-op
107.7 63.7
85 78
51, 57 72, 76
21 95
0 666
Baseline
67.7
71
51, 49
21
Intra-op
73.7
81
71, 70
100
0 166
Baseline
98
76
73, 67
21
Intra-op
73.3
89
82, 79
50
0 100
Baseline
90
77
64, 70
21
0
Intra-op
98.7
81
78, 89
97
67
Baseline
110.3
70
69, 65
21
0
Intra-op
83.7
81
90, 83
96
166.5
HR increased to 77 ± 8.8 bpm. This was an increase of 3 bpm (6 %, p = 0.29) compared with baseline. The average NTG rate was 220.4 ± 133.1 mcg/min. The average estimated blood loss was 467.5 ± 262.3 ml. NTG was titrated and patients were resuscitated to optimize rSO2 during controlled hypotension. The amount of crystalloid infused ranged from 1.5 to 6 L with an average
of 3.15 ± 1.25 L. Additionally, patients received 437.5 ± 312.8 ml of albumin. No ST changes were noted during the cases. The average starting rSO2 value was 65 ± 9 (L) and 68 ± 9 (R). After starting NTG, the average value increased to 79 ± 7 (L) and 78 ± 8 (R). This was an increase of 21.5 % (L, p \ 0.0001) and 14.7 % (R,
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J Clin Monit Comput (2014) 28:319–323
Table 3 Blood loss and fluid management #
EBL
Crystal
Albumin
pRBC
UOP 1,200
1
300
2,500
0
0
2
75
3,000
250
0
500
3
1,200
2,000
500
0
Field
4
600
3,000
500
1
600
5
300
3,400
500
4
500
6
700
6,000
250
0
2,000
7
150
3,000
0
0
1,000
8
325
2,000
250
0
650
9
700
3,500
500
3
850
10
550
2,500
250
0
700
11 12
450 250
3,500 1,600
500 500
0 0
600 700
13
450
3,000
250
0
500
14
250
2,000
750
2
400
15
550
2,000
0
2
450
16
200
4,000
1,250
0
1,850
17
500
5,500
500
0
1,000
18
800
1,500
1,000
0
1,125
19
400
4,500
500
0
800
20
600
4,500
500
2
1,600
Mean
467.5
3,150.0
437.5
0.7
896.1
SD
262.3
1,249.6
312.8
1.2
473.2
Table 4 Mean hemodynamic changes Baseline
Intra-op
%D
P
MAP
90 ± 14
72 ± 14
-19.5
\0.0001
HR
74 ± 9
77 ± 9
6.2
0.29
rSO2 (L)
65 ± 9
79 ± 7
21.5
\0.0001
rSO2 (R)
68 ± 9
78 ± 8
14.7
\0.0001
p \ 0.0001) compared with baseline (Table 2). While the rSO2 remained unchanged in two patients after starting the NTG infusion, no patients experienced a decrease in rSO2.
3 Discussion This case series illustrates that blood pressure alone is not a reliable marker of tissue perfusion as rSO2 increased even though MAP decreased. This concept has been validated in an animal model of gastric tube reconstruction following gastrectomy [13]. The authors found that while NTG significantly improved microvascular blood flow on laser Doppler flowmetry, increasing MAP with norepinephrine had no effect indicating that BP and perfusion are not always positively correlated.
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Perioperative hypovolemia is detrimental in that it results in a compensatory catecholamine release and a sympathetically mediated increase in peripheral vascular resistance in order to maintain MAP [14]. The detrimental physiologic effects including tissue vasoconstriction and microcirculatory maldistribution may be reversed with intravascular volume expansion using a combination of nitroglycerin and volume resuscitation. NTG dilates venous capacitance vessels, improves venous outflow, and increases tissue blood flow. For instance, during gastric tube reconstruction, NTG has been shown to double microvascular blood flow likely by ameliorating venous congestion [15]. Nitric oxide, the pharmacologically active component of NTG, inhibits platelet aggregation as well as being a potent vasodilator [16]. Nitric oxide is an important component of vascular protection. Through nitric oxide donation, NTG may mitigate endothelial dysfunction [17]. Indeed, NTG has been shown to protect the endothelium from ischemia and reperfusion injury [18]. Reversible platelet inhibition may also benefit perfusion. Many clinical examples illustrate that NTG improves tissue perfusion. NTG administration has been shown to both dilate intracranial arteries [19] and maintain cerebral pressure auto-regulation during controlled hypotension [20].It is well established that NTG decreases ischemia in unstable angina [21]. NTG has been shown to maintain splanchnic and overall organ perfusion when used for controlled hypotension [22]. NTG infusion has improved microvascular blood flow on orthogonal polarization spectral imaging in septic shock after volume resuscitation [23]. Finally, a NTG and fluids technique similar to the one used in this case series maintained tissue perfusion on transcutaneous oximetry and decreased the ARDS incidence from 16.6 % in the control group to 0 % in the study group during high-risk oncologic surgery [24]. While the nitroglycerin and IV fluids technique presented in this paper correlated with an increase in rSO2, there are several potential confounders. Volatile anesthetics are known to impair cerebral autoregulation [25]. As volatile anesthetics directly induce vasodilation while decreasing cerebral metabolic rate, they may lead to luxury perfusion at high concentration. Nitroglycerin, on the other hand, has been shown to maintain dynamic cerebral autoregulation [26]. It is possible that the volatile anesthetics used in the case series lead to luxury perfusion of the monitored area while diverting blood away from potentially ischemic regions. Therefore, rSO2 monitoring to ensure adequate cerebral perfusion in such a dynamic setting may be limited. An additional potential confounder in the study is that FiO2 was increased after induction. While patients were maintained on the same FiO2 throughout the case,
J Clin Monit Comput (2014) 28:319–323
increasing FiO2 alone could increase rSO2. However, after hemoglobin is saturated, increasing FiO2 increases the quantity of dissolved oxygen and contributes almost negligibly to overall oxygen content. Even if increased FiO2 did improve SpO2, there is no guarantee that it would improve microvascular blood flow or the health of the tissue. For example, following gastrectomy, impaired anastomotic healing is associated with decreased microvascular blood flow [27] but not with tissue PO2 [28]. In summary, this case series used cerebral oximetry to optimize each individual patient’s MAP by guiding NTG infusion rate and fluid administration during controlled hypotension. While infusing NTG, the MAP decreased 19.5 % from 90.3 mmHg to an average of 71.9 mmHg and rSO2 increased 21.5 % (L) and 14.7 % (R). These changes were statistically significant with p \ 0.0001. NTG, a potent venodilator, may improve cerebral oxygenation by increasing cerebral microvascular blood flow, improving cerebral perfusion through volume expansion, and ameliorating endothelial dysfunction and venous congestion.
References 1. Lessard MR, Trepanier CA, Baribault JP, Brochu JG, Brousseau CA, Cote JJ, Denault PH. Isoflurane-induced hypotension in orthognathic surgery. Anesth Analg. 1989;69:379–83. 2. Prielipp RC, Wall MH, Groban L, Tobin JR, Fahey FH, Harkness BA, Stump DA, James RL, Cannon MA, Bennett J, Butterworth J. Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers. Anesth Analg. 2001;93:45–52. 3. Choi WS, Samman N. Risks and benefits of deliberate hypotension in anaesthesia: a systematic review. Int J Oral Maxillofac Surg. 2008;37:687–703. 4. Strandgaard S. Autoregulation of cerebral blood flow in hypertensive patients. The modifying influence of prolonged antihypertensive treatment on the tolerance to acute, drug-induced hypotension. Circulation. 1976;53:720–7. 5. Meade P, Shoemaker WCC, Donnelly TJ, Abraham E, Jagels MA, Cryer HG, Hugli TE, Bishop WH, Wo CC. Temporal patterns of hemodynamic, oxygen transport, cytokine and complement activity in the development of adult respiratory distress syndrome after severe injury. J Trauma. 1994;36:651–7. 6. Casati A, Spreafico E, Putzu M, Fanelli G. New technology for noninvasive brain monitoring: continuous cerebral oximetry. Minerva Anesthesiol. 2006;72:605–25. 7. Tobias JD. Cerebral oxygenation monitoring: near-infrared spectroscopy. Expert Rev Med Devices. 2006;3:235–43. 8. Pollard V, Prough DS, DeMelo AE, Deyo DJ, Ucida T, Stoddart HF. Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo. Anesth Analg. 1996; 82:269–77. 9. Plachky J, Hofer S, Volkman M, Martin E, Bardenheuer HJ, Weigand MA. Regional cerebral oxygenation saturation is a sensitive marker of cerebral hypoperfusion during orthotopic liver transplantation. Anesth Analg. 2004;99:344–9. 10. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S. Monitoring
323
11.
12. 13.
14.
15.
16.
17. 18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007;104:51–8. Austin EH III, Edmonds HL Jr, Auden SM, Seremet V, Niznik G, Sehic A, Sowell MK, Cheppo CD, Corlett KM. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg. 1997;114:707–15. DeGoute CS. Controlled hypotension: a guide to drug choice. Drugs. 2007;67:1053–76. Van Bommel J, De Jonge J, Buise M, Specht P, Van Genderen M, Gommers D. The effect of intravenous nitroglycerin and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstruction. Surgery. 2010;148:71–7. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol. 1991;260:305–18. Buise M, Ince C, Tilanus H, Klein J, Gommers D, Van Bommel J. The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction. Anesth Analg. 2005;100:1107–11. Ignarro LJ, Ross G, Tillisch J. Pharmacology of endotheliumderived nitric oxide and nitrovasodilators. West J Med. 1991;154:51–62. Luscher TF. Vascular protection: current possibilities and future perspectives. Int J Clin Pract Suppl. 2001;117:3–6. Gori T, DiStolfo G, Sicuro S, Dragoni S, Lisi M, Forconi S, Parker JD. Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight. Br J Clin Pharmacol. 2007;64:145–50. Dahl A, Russell D, Nyberg-Hansen R, Rootwelt K. Effect of nitroglycerin on cerebral circulation measured by transcranial Doppler and SPECT. Stroke. 1989;20:1733–6. Endoh H, Honda T, Ohashi S, Hida S, Shibue C, Komura N. The influence of nicardipine, nitroglycerin, and prostaglandin E1 induced hypotension on cerebral pressure autoregulation in adult patients during propofol-fentanyl anesthesia. Anesth Analg. 2002;94:169–73. Karlberg KE, Saldeen T, Wallin R, Henriksson P, Nyquist O, Sylven C. Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. J Intern Med. 1998;243:25. Andel D, Andel H, Horauf K, Felfernig D, Millesi W, Zimpfer M. The influence of deliberate hypotension on splanchnic perfusion balance with use of either isoflurane or esmolol and nitroglycerin. Anesth Analg. 2001;93:1116–20. Spronk PE, Ince C, Gardien MJ, et al. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002;260:1395–6. Thangathurai D, Charbonnet C, Wo C, Shoemaker W, Mikhail M, Roffey P, Roessler P, Kuchta K, Zelman V, DeMeester T, Katz R. Intraoperative maintenance of tissue perfusion prevents ARDS. New Horiz. 1996;4:466–74. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology. 1995;83(1):66–76. Endoh H, Honda T, Ohashi S, Hida S, Shibue C, Komura N. The influence of nitroglycerin and prostaglandin E1 on dynamic cerebral autoregulation in adult patients during propofol and fentanyl anaesthesia. Anaesthesia. 2001;56(10):947–52. Miyazaki T, Kuwano H, Kato H, Yoshikawa M, Ojima H, Tsukada K. Predictive value of blood flow in the gastric tube in anastomotic insufficiency after thoracic esophagectomy. World J Surg. 2002;26:1319–23. Jacobi CA, Zieren HU, Zieren J, Muller JM. Is tissue oxygen tension during esophagectomy a predictor of esophagogastric anastomotic healing? J Surg Res. 1998;74:161–4.
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BRIEF REPORT
The use of regional cerebral oximetry monitoring during controlled hypotension: a case series Brandon A. Van Noord • Christopher L. Stalker Peter Roffey • Duraiyah Thangathurai
•
Received: 28 March 2013 / Accepted: 12 October 2013 / Published online: 18 October 2013 Ó Springer Science+Business Media New York 2013
Abstract Regional cerebral oximetry monitoring was used to guide nitroglycerin infusion and IV fluid administration during controlled hypotension in order to optimize each individual patient’s mean arterial pressure in a series of 20 consecutive patients who underwent major open urological or abdominal surgery. Although controlled hypotension offers a definite benefit in patients undergoing complex surgery where blood loss will be elevated or would severely compromise the surgical field, it is not without risk as low arterial pressure may compromise tissue perfusion and promote ischemia. In this case series, despite an average mean arterial pressure decrease of 19.5 % (p \ 0.001), cerebral oximetry values increased by an average of 22.7 % (p \ 0.001) after the nitroglycerin infusion had been initiated (220 mcg/min average). Patients received an average of 3.15L crystalloid and 437 ml albumin in fluid resuscitation. Keywords Controlled hypotension Nitroglycerin Cerebral oximetry
1 Introduction Controlled hypotension has been shown to decrease blood loss, decrease transfusion rate, and improve visibility of the surgical field [1]. Electively lowering mean arterial B. A. Van Noord C. L. Stalker P. Roffey D. Thangathurai Department of Anesthesia, Keck Medical Center, University of Southern California, Los Angeles, CA, USA B. A. Van Noord (&) Department of Anesthesiology, LAC?USC Medical Center, 1200 N. State St., IPT, Room C4E100, Los Angeles, CA 90033, USA e-mail: [email protected]
pressure (MAP) is not without risk as it may potentially decrease regional cerebral blood flow [2]. Therefore, general recommendations to maintain cerebral auto-regulation include maintaining MAP [ 55 mmHg [3] and lowering MAP \ 30 % from baseline in hypertensive patients [4]. Unfortunately, commonly utilized physiological monitors do not detect tissue ischemia directly. At best, blood pressure (BP), heart rate (HR), and pulse oximetry (SpO2) indirectly measure tissue oxygenation. SpO2 measures peripheral arterial blood oxygen saturation, not tissue oxygen tension itself. It is unable to compare tissue oxygen demand relative to supply or determine microvascular blood flow. Serial arterial blood gas (ABG) monitoring can demonstrate anaerobic metabolism and suggest ischemia. However, serial ABG monitoring is suboptimal as it is expensive, invasive, contributes to blood loss, and does not provide continuous real-time information. Due to the fact that tissue perfusion is difficult to assess clinically, the optimal BP for an individual patient is difficult to surmise. Indeed, tissue hypoxia, cellular injury, and inflammatory mediator release may occur even in the presence of normal MAP, HR, and SpO2 [5]. Cerebral oximetry (rSO2) is a new modality that uses near-infrared spectroscopy to penetrate the skull and continually and non-invasively measure the cerebrovascular perfusion in the tissue lying directly underneath sensors applied to the forehead [6]. The single numerical value displayed combines venous (75 %) and arterial (25 %) blood volume saturations [7]. Validation studies have shown that rSO2 provides information on cerebral desaturation that is as accurate as information obtained invasively [8]. For example, during orthotopic liver transplantation, rSO2 desaturation correlated with biochemical markers of cerebral hypo-perfusion while hemodynamic variables did not [9].
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Clinically, rSO2 measurement allows the brain to be used as an index organ to assess global oxygenation and tissue perfusion. Theoretically, systemic benefits should be seen if cerebral deoxygenation is prevented during surgery. Recent prospective studies have shown this to be true. In patients undergoing CABG, maintaining cerebral oximetry greater than 75 % was associated with a lower incidence of postoperative ventilation [48 h, stroke, myocardial infarction, and repeat surgery [10]. In pediatric patients undergoing cardiopulmonary bypass to repair congenital cardiac anomalies, interventions based on rSO2 monitoring decreased postoperative neurological sequelae and length of stay [11]. While multiple agents may be used for controlled hypotension, nitroglycerin (NTG) is our agent of choice. NTG dilates venous capacitance vessels, has a short halflife, does not produce clinically toxic metabolites, and is not associated with a rebound phenomenon. As NTG may induce hypotension by increasing venous blood volume and reducing venous return, patients must be adequately volume resuscitated to maintain blood flow and prevent an adrenergic response [12].
2 Case series We report on 20 consecutive cases between January 12 and February 22, 2012. Institutional Review Board approval was obtained prior to case review. One-sample student’s t test was used to compare means [BMDP statistical software, version 8.1 (Statistical Solutions, Los Angeles, CA)]. Continuous variables are presented as mean ± standard deviation. A value of p B 0.05 was considered statistically significant. The same anesthetic team performed all cases and managed all patients post-operatively in the ICU. Anesthesia was induced with propofol, fentanyl, and ketamine and maintained with a low dose inhalational agent such as isoflurane in an air-oxygen mixture along with supplemental doses of ketamine and fentanyl. Depending on underlying renal function, muscle relaxation was produced with vecuronium or cisatricurium. In addition to standard ASA monitors, an arterial line was placed. NTG infusion, crystalloids, and colloids were titrated to maximize recorded rSO2. Baseline (pre-NTG) MAP, HR, rSO2, and FiO2 values were obtained prior to induction while the patient was breathing room air. The intra-op MAP, HR, rSO2, and FiO2 values were recorded during steady state anesthetic conditions. The FiO2 remained constant throughout the case with the only variable being the NTG infusion rate. The majority of patients were extubated prior to ICU transport. Post-operatively, the same intra-operative NTG dose was initially maintained. Patient demographics are presented in Table 1. The typical patient was an elderly male admitted for a radical
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J Clin Monit Comput (2014) 28:319–323
cystectomy: 17 patients were male, the average age was 66, and 13 cases involved bladder excision for tumor. Patient 1 was a 26 year-old male Jehovah’s Witness who presented for excision of massive retroperitoneal metastases. He had previously received bleomycin for testicular cancer. Using rSO2 to guide NTG titration and fluid administration allowed for more aggressive decrease in blood pressure and resulted in an estimated intraoperative blood loss of only 300 ml. He was extubated at the end of the procedure and recovered uneventfully. Patient 16 was a 61 year-old male who underwent radical nephrectomy and caval thrombectomy. With the aid of the hypotensive technique described in this paper, blood loss was minimized to 200 ml and rSO2 increased 37 % during surgery. Hemodynamic changes, blood loss, and fluid management are presented in Tables 2 and 3. Mean hemodynamic changes are presented in Table 4 along with statistical significance. The average starting MAP was 90.3 ± 13.7 mmHg. After starting NTG, the average MAP decreased to 71.9 ± 14.3 mmHg intra-op. This represented an average decrease of 17.5 mmHg (19.5 %, p \ 0.0001) during surgery compared with baseline. Interestingly, the MAP actually increased in two patients after NTG initiation and adequate fluid resuscitation. The average starting HR was 74.3 ± 9.4 bpm. After starting NTG, the average
Table 1 Patient demographics #
Gender
Age
Procedure
1
M
26
RPLND and metastatic tumor excision
2
F
65
Robotic partial nephrectomy
3 4
F M
62 57
Radical cystectomy Radical cystectomy
5
M
81
Radical cystectomy
6
M
57
Radical cystectomy
7
M
33
B/L robotic partial nephrectomy
8
M
72
Radical cystectomy ? RPLND
9
M
80
Radical cystectomy
10
M
79
Radical cystectomy ? RPLND
11
M
86
Radical cystectomy ? RPLND
12
F
67
LAR for rectal cancer
13
M
72
Cystoprostatectomy, RPLND
14
M
67
Nephrouretectomy ? RPLND
15
M
84
Cystoprostatectomy, RPLND
16
M
61
Radical nephrectomy ? caval thrombectomy
17
M
64
Radical cystectomy ? RPLND
18
M
67
Radical cystectomy ? RPLND
19
M
70
Cystoprostatectomy, RPLND
20
M
66
Radical nephrectomy
RPLND retro-peritoneal lymph node dissection, LAR low abdominal resection
J Clin Monit Comput (2014) 28:319–323 Table 2 Hemodynamic changes
321
# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
MAP (mmHg)
HR (bpm)
rSO2 (L,R)
FiO2 (%)
NTG (mcg/min)
Baseline
73.3
86
77,78
21
Intra-op
56.3
64
77, 78
21
166
Baseline
78.7
75
76, 80
21
0
Intra-op
63
66
78, 85
100
Baseline
91
90
75, 74
21
0
333 0
Intra-op
56.7
76
88, 88
100
Baseline
80
70
78, 58
21
166
Intra-op
49.7
96
89, 68
56
333
Baseline
79
64
54, 57
21
0
Intra-op
74.7
78
69, 70
62
266 0
0
Baseline
89.3
81
54, 48
21
Intra-op
79.7
71
71, 69
50
233
Baseline
110.3
65
73, 68
21
0
Intra-op
55
69
84, 78
79
66
Baseline Intra-op
83 79.3
59 66
58, 60 78, 81
21 50
0 233 0
Baseline
92.3
62
59, 59
21
Intra-op
83.3
63
72, 73
60
333
Baseline
104.3
76
63, 63
21
0
Intra-op
87.3
84
80, 79
100
Baseline
68
65
65, 65
21
133 0
Intra-op
48
72
85, 83
100
Baseline
79.3
94
67, 64
21
249
Intra-op
69
88
67, 64
62
166.5
Baseline
101
76
77, 79
21
0
0
Intra-op
92.3
82
90, 95
75
166.5 0
Baseline
104.3
75
64, 60
21
Intra-op
83.7
78
79, 86
96
266
Baseline
98.3
69
55, 55
21
0
Intra-op
67.3
78
71, 69
97
133
Baseline Intra-op
107.7 63.7
85 78
51, 57 72, 76
21 95
0 666
Baseline
67.7
71
51, 49
21
Intra-op
73.7
81
71, 70
100
0 166
Baseline
98
76
73, 67
21
Intra-op
73.3
89
82, 79
50
0 100
Baseline
90
77
64, 70
21
0
Intra-op
98.7
81
78, 89
97
67
Baseline
110.3
70
69, 65
21
0
Intra-op
83.7
81
90, 83
96
166.5
HR increased to 77 ± 8.8 bpm. This was an increase of 3 bpm (6 %, p = 0.29) compared with baseline. The average NTG rate was 220.4 ± 133.1 mcg/min. The average estimated blood loss was 467.5 ± 262.3 ml. NTG was titrated and patients were resuscitated to optimize rSO2 during controlled hypotension. The amount of crystalloid infused ranged from 1.5 to 6 L with an average
of 3.15 ± 1.25 L. Additionally, patients received 437.5 ± 312.8 ml of albumin. No ST changes were noted during the cases. The average starting rSO2 value was 65 ± 9 (L) and 68 ± 9 (R). After starting NTG, the average value increased to 79 ± 7 (L) and 78 ± 8 (R). This was an increase of 21.5 % (L, p \ 0.0001) and 14.7 % (R,
123
322
J Clin Monit Comput (2014) 28:319–323
Table 3 Blood loss and fluid management #
EBL
Crystal
Albumin
pRBC
UOP 1,200
1
300
2,500
0
0
2
75
3,000
250
0
500
3
1,200
2,000
500
0
Field
4
600
3,000
500
1
600
5
300
3,400
500
4
500
6
700
6,000
250
0
2,000
7
150
3,000
0
0
1,000
8
325
2,000
250
0
650
9
700
3,500
500
3
850
10
550
2,500
250
0
700
11 12
450 250
3,500 1,600
500 500
0 0
600 700
13
450
3,000
250
0
500
14
250
2,000
750
2
400
15
550
2,000
0
2
450
16
200
4,000
1,250
0
1,850
17
500
5,500
500
0
1,000
18
800
1,500
1,000
0
1,125
19
400
4,500
500
0
800
20
600
4,500
500
2
1,600
Mean
467.5
3,150.0
437.5
0.7
896.1
SD
262.3
1,249.6
312.8
1.2
473.2
Table 4 Mean hemodynamic changes Baseline
Intra-op
%D
P
MAP
90 ± 14
72 ± 14
-19.5
\0.0001
HR
74 ± 9
77 ± 9
6.2
0.29
rSO2 (L)
65 ± 9
79 ± 7
21.5
\0.0001
rSO2 (R)
68 ± 9
78 ± 8
14.7
\0.0001
p \ 0.0001) compared with baseline (Table 2). While the rSO2 remained unchanged in two patients after starting the NTG infusion, no patients experienced a decrease in rSO2.
3 Discussion This case series illustrates that blood pressure alone is not a reliable marker of tissue perfusion as rSO2 increased even though MAP decreased. This concept has been validated in an animal model of gastric tube reconstruction following gastrectomy [13]. The authors found that while NTG significantly improved microvascular blood flow on laser Doppler flowmetry, increasing MAP with norepinephrine had no effect indicating that BP and perfusion are not always positively correlated.
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Perioperative hypovolemia is detrimental in that it results in a compensatory catecholamine release and a sympathetically mediated increase in peripheral vascular resistance in order to maintain MAP [14]. The detrimental physiologic effects including tissue vasoconstriction and microcirculatory maldistribution may be reversed with intravascular volume expansion using a combination of nitroglycerin and volume resuscitation. NTG dilates venous capacitance vessels, improves venous outflow, and increases tissue blood flow. For instance, during gastric tube reconstruction, NTG has been shown to double microvascular blood flow likely by ameliorating venous congestion [15]. Nitric oxide, the pharmacologically active component of NTG, inhibits platelet aggregation as well as being a potent vasodilator [16]. Nitric oxide is an important component of vascular protection. Through nitric oxide donation, NTG may mitigate endothelial dysfunction [17]. Indeed, NTG has been shown to protect the endothelium from ischemia and reperfusion injury [18]. Reversible platelet inhibition may also benefit perfusion. Many clinical examples illustrate that NTG improves tissue perfusion. NTG administration has been shown to both dilate intracranial arteries [19] and maintain cerebral pressure auto-regulation during controlled hypotension [20].It is well established that NTG decreases ischemia in unstable angina [21]. NTG has been shown to maintain splanchnic and overall organ perfusion when used for controlled hypotension [22]. NTG infusion has improved microvascular blood flow on orthogonal polarization spectral imaging in septic shock after volume resuscitation [23]. Finally, a NTG and fluids technique similar to the one used in this case series maintained tissue perfusion on transcutaneous oximetry and decreased the ARDS incidence from 16.6 % in the control group to 0 % in the study group during high-risk oncologic surgery [24]. While the nitroglycerin and IV fluids technique presented in this paper correlated with an increase in rSO2, there are several potential confounders. Volatile anesthetics are known to impair cerebral autoregulation [25]. As volatile anesthetics directly induce vasodilation while decreasing cerebral metabolic rate, they may lead to luxury perfusion at high concentration. Nitroglycerin, on the other hand, has been shown to maintain dynamic cerebral autoregulation [26]. It is possible that the volatile anesthetics used in the case series lead to luxury perfusion of the monitored area while diverting blood away from potentially ischemic regions. Therefore, rSO2 monitoring to ensure adequate cerebral perfusion in such a dynamic setting may be limited. An additional potential confounder in the study is that FiO2 was increased after induction. While patients were maintained on the same FiO2 throughout the case,
J Clin Monit Comput (2014) 28:319–323
increasing FiO2 alone could increase rSO2. However, after hemoglobin is saturated, increasing FiO2 increases the quantity of dissolved oxygen and contributes almost negligibly to overall oxygen content. Even if increased FiO2 did improve SpO2, there is no guarantee that it would improve microvascular blood flow or the health of the tissue. For example, following gastrectomy, impaired anastomotic healing is associated with decreased microvascular blood flow [27] but not with tissue PO2 [28]. In summary, this case series used cerebral oximetry to optimize each individual patient’s MAP by guiding NTG infusion rate and fluid administration during controlled hypotension. While infusing NTG, the MAP decreased 19.5 % from 90.3 mmHg to an average of 71.9 mmHg and rSO2 increased 21.5 % (L) and 14.7 % (R). These changes were statistically significant with p \ 0.0001. NTG, a potent venodilator, may improve cerebral oxygenation by increasing cerebral microvascular blood flow, improving cerebral perfusion through volume expansion, and ameliorating endothelial dysfunction and venous congestion.
References 1. Lessard MR, Trepanier CA, Baribault JP, Brochu JG, Brousseau CA, Cote JJ, Denault PH. Isoflurane-induced hypotension in orthognathic surgery. Anesth Analg. 1989;69:379–83. 2. Prielipp RC, Wall MH, Groban L, Tobin JR, Fahey FH, Harkness BA, Stump DA, James RL, Cannon MA, Bennett J, Butterworth J. Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers. Anesth Analg. 2001;93:45–52. 3. Choi WS, Samman N. Risks and benefits of deliberate hypotension in anaesthesia: a systematic review. Int J Oral Maxillofac Surg. 2008;37:687–703. 4. Strandgaard S. Autoregulation of cerebral blood flow in hypertensive patients. The modifying influence of prolonged antihypertensive treatment on the tolerance to acute, drug-induced hypotension. Circulation. 1976;53:720–7. 5. Meade P, Shoemaker WCC, Donnelly TJ, Abraham E, Jagels MA, Cryer HG, Hugli TE, Bishop WH, Wo CC. Temporal patterns of hemodynamic, oxygen transport, cytokine and complement activity in the development of adult respiratory distress syndrome after severe injury. J Trauma. 1994;36:651–7. 6. Casati A, Spreafico E, Putzu M, Fanelli G. New technology for noninvasive brain monitoring: continuous cerebral oximetry. Minerva Anesthesiol. 2006;72:605–25. 7. Tobias JD. Cerebral oxygenation monitoring: near-infrared spectroscopy. Expert Rev Med Devices. 2006;3:235–43. 8. Pollard V, Prough DS, DeMelo AE, Deyo DJ, Ucida T, Stoddart HF. Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo. Anesth Analg. 1996; 82:269–77. 9. Plachky J, Hofer S, Volkman M, Martin E, Bardenheuer HJ, Weigand MA. Regional cerebral oxygenation saturation is a sensitive marker of cerebral hypoperfusion during orthotopic liver transplantation. Anesth Analg. 2004;99:344–9. 10. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S. Monitoring
323
11.
12. 13.
14.
15.
16.
17. 18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007;104:51–8. Austin EH III, Edmonds HL Jr, Auden SM, Seremet V, Niznik G, Sehic A, Sowell MK, Cheppo CD, Corlett KM. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg. 1997;114:707–15. DeGoute CS. Controlled hypotension: a guide to drug choice. Drugs. 2007;67:1053–76. Van Bommel J, De Jonge J, Buise M, Specht P, Van Genderen M, Gommers D. The effect of intravenous nitroglycerin and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstruction. Surgery. 2010;148:71–7. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol. 1991;260:305–18. Buise M, Ince C, Tilanus H, Klein J, Gommers D, Van Bommel J. The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction. Anesth Analg. 2005;100:1107–11. Ignarro LJ, Ross G, Tillisch J. Pharmacology of endotheliumderived nitric oxide and nitrovasodilators. West J Med. 1991;154:51–62. Luscher TF. Vascular protection: current possibilities and future perspectives. Int J Clin Pract Suppl. 2001;117:3–6. Gori T, DiStolfo G, Sicuro S, Dragoni S, Lisi M, Forconi S, Parker JD. Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight. Br J Clin Pharmacol. 2007;64:145–50. Dahl A, Russell D, Nyberg-Hansen R, Rootwelt K. Effect of nitroglycerin on cerebral circulation measured by transcranial Doppler and SPECT. Stroke. 1989;20:1733–6. Endoh H, Honda T, Ohashi S, Hida S, Shibue C, Komura N. The influence of nicardipine, nitroglycerin, and prostaglandin E1 induced hypotension on cerebral pressure autoregulation in adult patients during propofol-fentanyl anesthesia. Anesth Analg. 2002;94:169–73. Karlberg KE, Saldeen T, Wallin R, Henriksson P, Nyquist O, Sylven C. Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. J Intern Med. 1998;243:25. Andel D, Andel H, Horauf K, Felfernig D, Millesi W, Zimpfer M. The influence of deliberate hypotension on splanchnic perfusion balance with use of either isoflurane or esmolol and nitroglycerin. Anesth Analg. 2001;93:1116–20. Spronk PE, Ince C, Gardien MJ, et al. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002;260:1395–6. Thangathurai D, Charbonnet C, Wo C, Shoemaker W, Mikhail M, Roffey P, Roessler P, Kuchta K, Zelman V, DeMeester T, Katz R. Intraoperative maintenance of tissue perfusion prevents ARDS. New Horiz. 1996;4:466–74. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology. 1995;83(1):66–76. Endoh H, Honda T, Ohashi S, Hida S, Shibue C, Komura N. The influence of nitroglycerin and prostaglandin E1 on dynamic cerebral autoregulation in adult patients during propofol and fentanyl anaesthesia. Anaesthesia. 2001;56(10):947–52. Miyazaki T, Kuwano H, Kato H, Yoshikawa M, Ojima H, Tsukada K. Predictive value of blood flow in the gastric tube in anastomotic insufficiency after thoracic esophagectomy. World J Surg. 2002;26:1319–23. Jacobi CA, Zieren HU, Zieren J, Muller JM. Is tissue oxygen tension during esophagectomy a predictor of esophagogastric anastomotic healing? J Surg Res. 1998;74:161–4.
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