inhalation anesth for cs

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)

Inhalation anestesia for caesarean section :why?

How?

C.Melloni

Servizio di Anestesia e Rianimazione

Ospedale di Faenza(RA)


Changes in obstetric anesthesia(C/S) in USA(Hawkins et al,Obstetric anesthesia workforce survey-1992 versus

1981.Anesthesiology 1994;81:A1128)

0%

10%20%30%40%

50%60%70%80%

90%100%

1981 1992

EpidSpiGA


Changes in obstetric anesthesia(C/S) in UK(Brown et al.Int J.Obstet.Anesth.1995;4:214)

0%

20%

40%

60%

80%

100%

1982 1987 1992

EpidSpiGA


Number of deaths during cesarean sectionNumber of deaths during cesarean sectionUSA 1979-1990(Hawkins et al.Anesthesiology 86;280:1997)USA 1979-1990(Hawkins et al.Anesthesiology 86;280:1997)

1979-19841979-1984 1985-19901985-1990

GAGA 3333 3232

REGREG 1919 99


Fatality rates during cesareansection

Fatality rates during cesareansection

per million of Ga or REGper million of Ga or REG

1979-19841979-1984 1985-19901985-1990

G.A.G.A. 2020 32.332.3

REGREG 8.68.6 1.91.9


Report on Confidential enquiries into maternal deaths in England and Wales 1970-1996

0

5

10

15

20

25

30

1970-72

73-75

76-78

79-81

82-84

85-87

88-90

91-93

94-96

Frequenza per milione di gravid.stimate

emb.polmipertens

anestemb.fluido amniotico

abortogravid.ectopica

emorragiasepsi

rottura uteroaltre cause dirette

Entrata in vigore della nuova classificazione


Tsen LC, Camann W (2000) Training in obstetric general

anaesthesia: a vanishing art?Anaesthesia. 55:179-83


Topics� Indications� Contraindications� Side effects� Transplacentar passage:

» effects on the fetus and neonate� potentiating GA:reasons for:catecholamine reduction……

Crawford??� Obstetrical manoeuvers…� Emergency CS� Awareness avoidance—closed claims….� How:nearly all halogenated are equal…MAC properties� Side effects� Hypotension…but avoidance of aortocaval compression…� Nausea & vomiting� PONV� Difficult intubations…� Induction in patients with no iv access.� Uterine atony..


Indications for GA in OBS� Anesthesia personnel inexperienced in providing regional

anesthesia� Patient refusal of reg� Patient not cooperative� any istance of contraindications to regional anesth:

» infection:localized(dorsum) vs generalized(sepsis)….» Coagulopathy:

� emergency:foetal distress,placenta praevia,maternal haemorrhage, urgent obstetrical manoeuvers …….

� Hypovolemia….� Certain forms of heart disease that cannot tolerate

hypotension:fixed cardiac output;e.g.severe aortic stenosis,Eisenmenger syndr.


Parekh N,Husaini SWU,Russell IFCaesarean section for placenta praevia:a retrospective study of anesthetic

management.Br.J.Anaesth. 2000;84:723-30.

� All anesth from 1 genn 1984 to 31/12/1998.� 350 cases of plac previa:

» 60% Reg / 40% AG» plc accreta;7 cases; 4 REG , 3 AG:but 2 reg convert.to

AG…5 hysterect.» PA control during haemorrhage not a problem» Ra assoc.with less blood loss» “This retropectuve study do not support the often quoted

motto that plac.praevia calls for AG….”.


Disadvantages of GA� Asleep & unaware(late maternal bonding…)� husband less likely to be allowed in OR� drug depression of fetus� stress response to intubation� increased postoperative morbidity� cardiovascular changes of intubation� danger of aspiration(intubation & extubation)� difficult intubation


Ga:technique:I� Premed;antacids/H2 blockers/sodium citrate� LUD� ID/ UI-D intervals as short as possible� preoxygenation� (precurarization)� induction� cricoid pressure� Succi


Ga:technique:II� IOT� check lung expansion,bilat.� N20 50% + halog 0.6 Mac� after delivery:repeat hypnotic + analgesic;stop volatile� Oxytocin 10-20 UI/lt,drip…� extubate awake and cooperative,having ascertained

the full return of nm function…� plan for failed intubation


Indications for halogenated anesthetics

� potentiating GA:reasons for:catecholamine reduction……Crawford??

� Reduction or avoidance of maternal awareness,patient asleep and unaware

� optimum operating conditions


Side effects

� Haemodynamics derangement� uterine atonia…


Halogenated agents:advantages..

� allow use of increased O2 concentrations

� may increase uterine blood flow by decreasing maternal catecholamine mediated uterine artery constriction

� prevents awareness…but a few minutes are needed before the attainment of a reasonable MAC…(sevorane or desflurane more rapid equilibration!


Halogenated agents:diasdvantages..

� Uterine bleeding� low apgar scores?� Low neuroehavioral examinations� theatre pollution...


Modifications that affect inhalation anesthesia in pregnancy

� pain and discomfort thresholds

� MAC requirements 25% 40%.‑� FRC


Transfer time


Mac and pregnancy

� Mac for inhalational agents decresed by pregnancy(Datta et al,Chronically administered progesterone decreases halothane requirements in rabbits.Anesth.Analg. 1989;68:46-50)


Chan et al.Minimum Alveolar Concentration of Halothane and

Enflurane Are Decreased in Early Pregnancy Anesthesiology85:782-6, 1996


MAC reduction in pregnancy Gin T, Chan MTV: Decreased minimum alveolar concentration of isoflurane in pregnant humans.

ANESTHESIOLOGY 81:829-32, 1994 ;& Chan et al.Minimum Alveolar Concentration of Halothane and Enflurane Are Decreased in Early Pregnancy

Anesthesiology 85:782-6, 1996

0

0,2

0,4

0,6

0,81

1,2

1,4

1,6

1,8

non pregnant pregnant

isofluranehalothaneenflurane


Avoid maternal hyperventilation


King H, Ashley S, Brathwaite D, Decayette J, Wooten D: Adequacy of general anesthesia for cesarean section. Anesth Analg 77:84-8, 1993

020406080

100120

lryn

gosc

opy,

IOT

skin

inc

1 m

in

2min

3min

% of patients

Lifescanfinger flexionhand squeezelacrimation

Isolated arm technique

Tps/scc/iot/N2O 50/haloth 0.5%

ind inc

68-130 sec

delivery220-367 sec.


Characteristics of inhaledanesthetics

Decomposesnone2,424150,20,75197,4halothane

Stablemoderate

1,917556.51,68184,5enflurane

Stablemoderate

1.423848.51.15184,5isoflurane

decomposesno0,6016058.52.0200sevoflurane

stableno0,4739000gas

-8810544N2O

stableyes0,4266323.56168desflurane

Soda limepungencyBlood/gaspartitioncoeff.

Vaporpress.

Bolingpoint

MACmwagent


Rise in alveolar(Fa) anesthetic concentration toward the inspired(Fi) concentration


Navarro EM.Desflurane general anesthesia for cesarean section compared with isoflurane and epidural

anesthesia.Anesthesiol.Intensivmed.Notfallmed.Schmerzther 2000;35;232-6.

� Desflurane 2.5% vs isofl 0.5% vs epid 15 ml ropi 0.75% + fent 100 microgr

� N2O 50%� intraop haemodynamics� blood loss� maternal awareness� Apgar scores 1-5 min� NACS 2-24 h� Ega UV/MV


Navarro II

� No diff among the 3 groups except a more rapid emergence following des.


Olthoff D,Rohrbach A. Sevoflurane in obstetric anesthesia.Anesthesist 1998;47,suppl 1,s 63-9

� Sevo > isofl and no outcome diff with epid,

� sevo> isof in pEEG monitoring……...


Transplacentar passage


Attenuation of catecholamine responses……..


Shnider et al: Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe.

ANESTHESIOLOGY 50:524-7, 1979

-80

-60

-40

-20

0

20

40

60

1 2 3 4 5

min

% change from basal

MAPNorepiuter.Blood flow

\

Electrically induced stress 30-60 sec,loud noises,sudden movement of personnel...


Uterine blood flow changes during anesth.in the pregnant ewe(from

Shnider,Levinson,etc..)

-20-15-10

-505

101520

% change from control

anest without stim anest withstimulation

N2O 50%N2O 50% +haloth 0.5%N2O 50% + enfl 1%


Maternal awareness of surgery and birth after barbiturate-relaxant induction &...

02468

101214161820

%

maternal awareness

N2O 50%

N2O 67-75%

N2O 25-40%+halo0.4%N2O 50%+haloth0.3%N2O 50%+enfl 0,75

N2O 33%+metx 0.1%

N2O 50+ isof 0,75%


Lyons G, Macdonald R: Awareness during caesarean section. Anaesthesia 46:62-4, 1991

� 1982-1989 � > 3000 patients � questioned about recall and dreaming after general

anaesthesia for Caesarean section� 28 (0.9%) patients were able to recall something of

their operation � 189 (6.1%) reported dreams. Recollections of surgery

were confined to manipulations, noises and voices. None of our patients complained of pain at the time of interview, although one since has.


Incidence of awareness(from various sources)

0

2

4

6

8

10

12

14

16

%

incidence

C/Scard.surgnon card. Surgmajor trauma

0.4


Domino K, Posner KL, Caplan, R,Cheney F. Awareness during Anesthesia : A Closed Claims Analysis.Anesthesiology

90:1053-61, 1999.

Liability risk


Closed claim database for intraoperative awareness

� 79 over 4183 claims;1.9% :» 18 claims for awake paralysis(inadvertent paralysis of

an awake patient

» 61 claims for recall during GA :recall of events while receiving general anesthesia


Awareness claims

� 1.9% of all claims� awareness, defined as being paralyzed

while awake or awake while receiving a general anesthetic, were reviewed. These claims were further divided into two categories: awake paralysis, i.e., the inadvertent paralysis of an awake patient, and recall during general anesthesia, i.e., patient recalled events while receiving general anesthesia.


Closed claim database for intraoperative awareness

� The majority of awareness claims involved :» women (77%)(OR 3.21)

» younger than 60 yr of age (89%)

» ASA I—II (68%)» who underwent elective surgery (87%),obs/gynecol.

� Claims for recall during general anesthesia were more likely to involve :» women (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06)

� anesthetic techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74)

� intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25)

� and no volatile anesthetic (OR = 3.20, 95% CI = 1.88, 5.46).


Dwyer R, Bennett HL, Eger EI II, Peterson N: Isoflurane anesthesia prevents unconscious learning. Anesth Analg

75:107-12, 1992

� Several authors report prevention of conscious recall of events by relatively small concentrations of volatile anesthetics. Isoflurane in concentrations of 0.6 MAC prevented conscious recall and unconscious learning of factual information and behavioral suggestions.


Ranta S, Laurila R,Saario J,Ali-Melkkilä T, Hynynen M. Awareness with Recall During General Anesthesia: Incidence

and Risk Factors Anesth Analg 1998; 86:1084 � 4818 operations under GA: 2612 (54%) patients were

interviewed� 10 (0.4% of those interviewed) patients were found to

have undisputed awareness� 9 (0.3%) patients with possible awareness.� The doses of isoflurane (P < 0.01) and propofol (P <

0.05) were smaller in patients with awareness.� 5 patients with awareness underwent a psychiatric

evaluation;possible associtation with depression. � 1 patient experienced sleep disturbances afterward,

but the other four patients did not have any after effects.


Moir, D. D .ANAESTHESIA FOR CAESAREAN SECTION An Evaluation of a Method using Low Concentrations of Halothane and 50 per cent of Oxygen Br. J. Anaesth. 1998; 80:690-696

� The addition of 0.5 per cent of halothane vapour to a basic thiopentone, nitrous oxide, muscle relaxant anaesthetic technique does not increase blood loss at Caesarean section, does not affect the incidence of hypotension, and is likely to ensure unconsciousness. By permitting the administration of 50 per cent of oxygen with nitrous oxide, the condition of the newborn infant is likely to be improved. The use of 0.8 per cent of halothane vapour does not increase blood loss but is associated with a high incidence of hypotension and for this reason is not advisable.


Elective C/S:Duration of GA or Epidural antepartum and % of

Apgar scores between 7-10 (da dati di Robin,Shnider,Levinson---)

0102030405060708090

100

% 7-10 Apgar scores

GA epid

<5

6;10

11;20

21;30

31;60

Min:


I-D & UI-D

� But more importantly than overall duration between induction and delivery

(I-D) is the

� uterine incision-delivery interval(UI-D),that has been shown to correlate with fetal hypoxia and acidosis


GA and neonatal depression

0102030405060708090

100

Apgar 1' Apgar 5'

spinalepiduralGA


Fetal-neonatal effects of halogenated vapours

� ONG BY,Cohen MM,Palahniuk RJ:Anesthesia for cesarean section: effects on neonates.Anesth.Analg 1989;68:270-275.

� Greater requirements for neonatal intubation and resuscitation versus regional block in urgent C/S


Ong BY,Cohen MM,Palahniuk RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

� 3940 C/S;12.5% of neonates Apgar < 4� 1.5% 5 min Apgar score < 4� list of factors associated with low 1 min Apgar scores:� primiparity� grand multiparity� antepartum disease(preeclampsia,diabetes mellitus,maternal heart disease RH

isoimmunization, early amtepartum haemorrhage)� presence of fetal distress� low gestational age� use of narcotics during labor� breech presentation� nonelective C/S� GA


Ong et al.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

� Multivariate analysis that controlled for many variables gave:

� Higher risk of low apgar at 1 min GA 3 >reg(2.5-3.88)

� Higher risk of low Apgar at 5 min; GA 3> reg(1.81-7)

� need for resuscitation: GA 2> reg(1.32-2.90)


Neonatal outcome after C/S by anesthetic technique:infants

with 1 min Apgar score < 4 (%) Ong BY,Cohen MM,Palahniuk RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

0

5

10

15

20

25

30

35

40

45

reg GA

electivefetal distressfailure to progress

0.05

0.01

0.001


Infants with 5 min Apgar score 0-4(%) Ong BY,Cohen MM,Palahniuk

RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

0

1

2

3

4

5

6

7

8

9

reg GA


0.01

0.01


Neonates requiring oxygen by mask(%) Ong BY,Cohen MM,Palahniuk RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

0

5

10

15

20

25

reg GA


0.01

0.001


Neonates requiring iot and IPPV(%) Ong BY,Cohen MM,Palahniuk RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

40,0

45,0

reg GA


0.001


Gregory FA, Wagde JG, Biehl DR, Ong BY, Sitar DS. Foetal anaesthetic requirements (MAC) for halothane. Anesth Analg 1983;62:9 14.‑

Bachman CR, Biehl DR, Sitar DS, Cumming M, Pucci W. Isoflurane potency and cardiovascular effects during short exposures in the foetal lamb. Can Anaesth Soc

J 1986;33:41 7.‑

� MAC is significantly lower in fetal lambs than in lambs more than 24 hours of age.

� These findings suggest that neonates immediately after birth may be quite sensitive to inhalation anesthetics so that those exposed to general anesthetic agents may be less vigorous at birth. After assisted respirations and expiration of the anesthetic agents, these infants appear to resemble other infants,


Neonatal deaths Ong BY,Cohen MM,Palahniuk RJ.Anesthesia for cesarean section:effects on neonates.AA 1989;68:270-5.

0

1

2

3

4

5

6

7

reg GA



Postpartum blood loss:Piggott SE,Bogod DG,Rosen M,Rees GAD,Harmer M.Isoflurane with either 100% oxygen or 50%

nitrous oxide in oxygen for caesarean section.BJA 1990;65:325-29.

-25,0

-20,0

-15,0

-10,0

-5,0

0,0

HB decrease, %

N2O

50+h

alot

h0.

5

O21

00%

+h

alot

h0,

75

02 1

00%

+en

flu

r 1,

7

02 1

00%

+is

ofl

1,2%

electiveemergent


Influence of anesthesia on blood loss at C/S(Moir DD.Anesthesia for cesarean section:an evaluation of a method using low concentrations of halothane and 50% of

oxygen.BJA 1970;42:136-142.

0

100

200

300

400

500

600

700

800

ml

blood loss

N2O 70N2O50+ aloth 0,5N2O 50+ haloth 0,8epid analg


HCT values before and after C/S:(from Thirion et al.Maternal blood loss associated with low dose alothane administration for caesarean section.Anesthesiology

1988;69:a693)

0

5

10

15

20

25

30

35

40

%

halothpredelivery

aloth pre& post epidural

Hct preopHCTday 1Hct day 2


Conclusions for halog agents and blood loss

� Dose related decrease in uterine contractility and tone

� but no increase in blood loss if used in low-moderate concentrations:

� haloth 0.1-0.8� enflurane 0,5-1,5� isoflurane 0,75� sevoflurane…..


In every case,after delivery of the neonate…...

� Stop the volatile anesthetic� continue N2O(increase to 60-65%)� administer a IInd dose of hypnotic(TPS

100-150 mg;propofol 60-100 mg +� a potent analgesic:fentanyl 100-150

microgr..…� nmb if needed


Wojtczak, Jacek A., MD, PhDThe Hemodynamic Effects of Halothane and Isoflurane in

Chick Embryo Anesth Analg 2000; 90:1331

� The cardiovascular effects of volatile anesthetics in prenatal hearts are not well investigated. The purpose of this study was to determine whether the embryonic cardiovascular system is sensitive to an exposure to clinically relevant, equipotent concentrations of halothane and isoflurane. Stage 24 (4-day-old) chick embryos were exposed to 0.09 and 0.16 mM of halothane and 0.17 and 0.29 mM of isoflurane. Dorsal aortic blood velocity was measured with a pulsed-

Doppler velocity meter. Halothane, but not isoflurane, caused a significant decrease in cardiac stroke volume and maximum acceleration of blood (dV/dtmax), an index of cardiac performance. This effect was reversible, and during washout, stroke volume and dV/dtmax increased above control levels. Embryonic heart rate was not affected by either drug. Chick and human embryos are similar during early stages of development; therefore, chick embryo may be a useful model to study the cardiovascular effects of anesthetics.


Effect of halothane on stroke volume and acceleration of aortic blood in chick embryos


Effect of isoflurane on stroke volume and acceleration of aortic blood in chick embryos


Biehl DR, Tweed A, Cote J, et al. Effect of halothane on cardiac output and regional flow in the fetal lamb in utero.

Anesth Analg 1983; 62:489-92

� We studied the effect of halothane on the fetal cardiovascular system of six lambs in utero by measuring fetal heart rate and femoral arterial blood pressure and by injecting labeled microspheres during a control period and again after 60 and 90 min of halothane anesthesia administered to six pregnant ewes at an inspired concentration of 1.5%. There were no significant effects on maternal cardiovascular function or acid-base balance, but fetal blood pressure decreased significantly by 27% after 8 min of halothane anesthesia and remained at this level for the duration of the experiment. However, there were no significant changes either in fetal regional blood flow to the vital organs or in fetal cardiac output. Fetal oxygenation and acid-base status remained stable. We conclude that in normal fetal lamb in utero the decrease in mean fetal arterial blood pressure associated with maternal halothane anesthesia is due to a decrease in peripheral vascular resistance because regional blood flow and acid-base status are well maintained.


Biehl et al. Effect of halothane on cardiac output and regional flow in the fetal lamb in

utero. Anesth Analg 1983; 62:489-92

-40

-30

-20

-10

0

10

20

30

% change from control

8 16 32 60 96

min

MAPHRheart BFbrain BF

Halothane 1.5%

* * * * *


Bachman CR, Biehl DR, Sitar D, et al. Isoflurane potency and cardiovascular effects during short exposure in foetal lamb.

Can Anesth Soc J 1986; 33:41-7

� Isoflurane is a relatively new volatile anaesthetic in clinical practice and increasing use for obstetrical patients might be expected. A previous study demonstrated that a 60-90 minute exposure of the foetus to isoflurane resulted in a significant fall in foetal cardiac output with development of foetal acidosis. To determine the cardiovascular effects of a shorter exposure of the foetal lamb to isoflurane and the potency (MAC) of isoflurane in the foetus, the following study was done. Eleven pregnant ewes were surgically prepared by placing indwelling arterial and venous catheters into the mother and foetus. After a 48-hour recovery period, isoflurane, two per cent in oxygen, was administered to six ewes via a tracheostomy for 30 minutes. Foetal cardiac outputs and regional blood flows were measured by the microsphere method. In five ewes the concentration of isoflurane was varied and MAC determinations were done on both ewe and foetus. Arterial blood levels of isoflurane were used to determine foetal MAC. Exposure to isoflurane resulted in a significant decrease in maternal and foetal mean arterial blood pressures and in foetal heart rate. Exposures up to 30 minutes did not result in foetal acidosis or a significant fall in cardiac output. Maternal and foetal MAC for isoflurane were determined to be 0.86 and 0.34 per cent respectively.


Baum VC, Palmisano BW. The immature heart and anesthesia. Anesthesiology 1997; 87:1529-48

� volatile anesthetics inhibit myocardial function by depressing systems in addition to ICa,L even in neonatal myocardium. Baum and Wetzel showed that halothane, in clinically relevant concentrations, reversibly inhibits Na+—Ca2+ exchange in neonatal ventricular myocytes. This provides an additional mechanism that may be responsible for the more pronounced depression by volatile anesthetics of immature myocardium with its increased reliance on Na+—Ca2+ exchange.


Baum VC, Palmisano BW. The immature heart and anesthesia. Anesthesiology 1997; 87:1529-48

� Halothane and isoflurane prolong AV conduction time directly.

� Anesthesia and O2 Consumption and Metabolism

� In vitro, halothane and isoflurane increase coronary flow in a dose-related manner in infant rabbit and fetal lamb hearts. In the isolated heart preparation in which coronary perfusion pressure is constant, an increase in flow indicates a decrease in coronary vascular resistance and therefore direct vasodilatory actions of the agents on the coronary vessels. Changes in coronary flow are similar between newborn and adult hearts. Other in vitro studies have reported an increase in coronary flow by isoflurane and variable effects by halothane in adult animals. Reactivity of coronary vessels to other pharmacologic and metabolic stimuli have been demonstrated in newborn animals of several species.

� Isoflurane decreases O2 consumption and the O2 extraction ratio, which, coupled with increased coronary flow, indicates decreased autoregulation and relative overperfusion of the myocardium, demonstrable in newborn and adult hearts. Because it decreases heart rate more in adults, isoflurane decreases O2 consumption and extraction more in adults than in newborns. When heart rate is held constant by pacing, there are no differences in this effect between age groups.


Baum VC, Palmisano BW. The immature heart and anesthesia. Anesthesiology 1997; 87:1529-

48

� In the neonatal lamb undergoing hypoxic stress, neither halothane nor isoflurane alter redistribution of blood to vital organs, including the heart. In addition, myocardial blood flow in the neonatal lamb decreases significantly at 1 MAC isoflurane (from 250 to 88 ml×100 g-1×min-1), but in exact proportion to the decrease in myocardial oxygen consumption, allowing unchanged myocardial oxygen extraction and similar endocardial-to-epicardial myocardial flow ratios.



48

� In neonatal rabbit hearts studied in vitro with 1.5% halothane, McAuliffe and Hickey found no change in steady-state levels of high- energy phosphates or intracellular pH, despite a 50% decrement in mechanical performance. Significant uncoupling of oxidative phosphorylation cannot account for halothane's depressant effect on systolic function in the neonate.



48

� Anesthesia and Systolic Function� The effects of the inhalational

anesthetics in intact immature hearts have been evaluated in several studies. Although one study suggested that the apparent increase in hemodynamic depression in the young heart in human studies may be a result of differences in anesthetic uptake and distribution, other studies indicate the increased hemodynamic impairment of the volatile anesthetics is predominantly a result of increased direct myocardial depression in immature hearts. Cook et al., for example, showed that immature (aged 15 days) rats developed cardiovascular failure at significantly lower myocardial halothane concentrations than did older rats.

� Volatile anesthetics depress contractility primarily by limiting Ca2+ availability to the contractile apparatus. They alter transsarcolemma and sarcoplasmic reticulum Ca2+ flux with the net result that intracellular Ca2+ stores are depleted. Halothane depresses contractility more than isoflurane. It decreases peak intracellular Ca2+ concentration more than isoflurane, which may be a result of its greater depressant effect on sarcoplasmic reticulum function or on other mechanisms. In isolated rabbit hearts, halothane is a more potent depressant of contractile function (measured by peak systolic and developed LV pressures and +dP/dtMAX) than isoflurane in newborns and in adults. With isoflurane, there are no differential effects between age groups, whereas halothane causes greater depression in neonatal hearts. Other studies in rabbits have also found more depression by halothane of tension development in isolated RV tissue in newborns than adults and more inhibition of RV ventricular papillary muscle contractile function by halothane and isoflurane. In this case, inhibition was similar for both anesthetics. Other investigators have found an age differential in depression of contractility by isoflurane in isolated right atrial tissues of rat, but this may not be comparable with rabbit ventricle. This differential age effect may occur at many sites in the excitation—contraction mechanism, but little information regarding this is available.

� Several studies in the chronic neonatal lamb preparation have shown that halothane and isoflurane decrease cardiac output to a similar extent as oxygen consumption. Isoflurane at 1 MAC primarily decreased blood pressure by decreasing cardiac output rather than decreasing systemic vascular resistance. With hypoxemic stress, the isoflurane anesthetized lamb (1 MAC) responds by increasing cardiac output and oxygen delivery.



48

� Summary� Immature hearts are more profoundly

affected by many anesthetics than are adult hearts. Maturational changes in a variety of cellular and subcellular systems and influences of the autonomic nervous system may be responsible, but as yet, specific mechanisms remain to be elucidated. Studies of the interactions of anesthetics with the immature human heart are for the most part lacking, and extrapolation from other species is difficult. This is a fertile area for investigation, particularly for studies of the effects of the newer clinical anesthetics, which are lacking.


Brett CM, Teitel DF, Heymann MA, Rudolph AM: The young lamb can increase cardiovascular performance during

isoflurane anesthesia. ANESTHESIOLOGY 71:751-6, 1989

� Cardiac output and myocardial blood flow decrease dramatically in a dose-dependent pattern in the young lamb during isoflurane anesthesia. This raises important questions about the ability of the young lamb to increase myocardial performance if oxygen delivery were compromised by a decrease in oxygen content during anesthesia and surgery. To investigate the ability of the young lamb to increase oxygen delivery during isoflurane anesthesia, the response to hypoxemia, which is known to increase myocardial performance, was studied in awake 1-week-old lambs. Mean systemic arterial pressure, heart rate, cardiac output, and regional distribution of blood flow were measured during three states: awake, 1.0 minimum alveolar concentration (MAC) of isoflurane in an FIO2 of 1.0, and 1.0 MAC of isoflurane in an FIO2 of 0.09. Stroke volume, total body and myocardial oxygen consumption, and fractional extraction of oxygen were calculated for the total body and for the myocardium. Isoflurane anesthesia decreased mean systemic arterial pressure (70 +/- 8 mmHg), heart rate (222 +/- 29 beats/min), and cardiac output (277 +/- 72 ml.kg-1.min-1) significantly (43 +/- 11 mmHg, 163 +/- 20 beats/min, 191 +/- 34 ml.kg-1.min-1). Hypoxemia returned heart rate to control (191 +/- 23 beats/min), increased stroke volume (1.71 +/- 0.2 ml/kg) above both control (1.23 +/- 0.2 ml/kg) and 1.0 MAC isoflurane levels (1.19 +/- 0.3 ml/kg), and increased cardiac output (325 +/- 61 ml.kg-1.min-1) above the level during 1.0 MAC isoflurane.


Coagulation and anesthesia

� The Effect of Anesthetic Techniques on Blood Coagulability in Parturients as Measured by Thromboelastography

� Sharma, Shiv K., MD, FRCA; Philip, John, MD

� : Anesthetic techniques may affect blood coagulability and the subsequent incidence of thromboembolic events. The purpose of this study was to evaluate the effect of spinal and general anesthesia on blood coagulability in normal pregnant women undergoing cesarean section, using thromboelastography. In the spinal anesthesia group (n = 15), thromboelastography was performed after crystalloid preloading and during the immediate postanesthesia course. In the general anesthesia group (n = 15), thromboelastography was performed before induction and during the immediate postanesthesia course. Values for all thromboelastographic variables (reaction time [r], clot formation time [K], coagulation time [rK], maximum amplitude [MA], elastic shear modulus [G], clot formation rate [a angle], and coagulation index [CI]) in the preanesthesia period were similar in both the spinal and general anesthesia groups. However, in the postanesthesia period, r and K significantly decreased (P < 0.05), and a angle (P < 0.05) and CI significantly increased (P < 0.01) in the general anesthesia group when compared with the spinal anesthesia group. In the postanesthesia period, MA and G were similar in both groups. In the spinal anesthesia group, thromboelastographic variables did not change significantly in the postanesthesia compared with the preanesthesia period. We conclude that the use of general anesthesia for cesarean section is associated with accelerated coagulability when compared with spinal anesthesia.

� Anesth Analg 1997; 85:82–


Interactions of volatile agents with:

� nifedipine;enhancement of haemodynamic side effects with aloth,enfl,iso(but non pregnant animals…)..(and Rosone et al..Hemodynamic responses to nifedipine in dogs anesthetized with halothane. Anesth.Analg 1983;62:903-908.)

� nicardipine enhancement of uterine atony not easily reversible post partum with oxitocin: Csapo et al.Deactivation of the uterus during normal and premature labor by the calcium antagonist nicardipine.Am,J.Obstet.Gynecol. 1982;142:483-91


� “Progesterone Decreases the MAC of Desflurane in the Non Pregnant Ewe,” was presented by Thompson and collaborators, Ochsner Clinic, New Orleans. They noted that the minimum alveolar concentration for pregnant ewes and that for nonpregnant ewes treated with progesterone were similar. The minimum alveolar concentration of desflurane in untreated nonpregnant ewes was greater than in the other two groups.


� Inhalational anesthetics with a rapid equilibration between inspiratory and end tidal concentraions,i.e less soluble,should provide the correct answer…..


WarrenTJ,Datta S,Osrheimer GW et al. Comparison of the maternal and neonatal effects of

hsalothane,enflurane and isoflurane for cesarean delivery.Anesth.Analg 1983;62:516-520.


Datta et al.Maternal and fetal catecholamines and uterine incision-delivery interval during elective cesarean

section.Obstet.Gynecol 1990;75:600-603.


Neurobehavioral examination

� Results more depressed(albeit subtle) in neonates born from GA than reg….(Shnider 238 pagg…)


Wallace DH et al.Randomized comparison of regional and general anesthesia for cesarean delivery in pregnancies

complicated by severe preeclampsia.Obstet Gynecol

1995;86,193-


Gin T, Chan MTV: Decreased minimum alveolar concentration of isoflurane in pregnant humans.

ANESTHESIOLOGY 81:829-32, 1994

� <AB - BACKGROUND: Minimum alveolar concentration (MAC) is decreased in pregnant animals, but this change has not been demonstrated in humans, probably because of ethical considerations. It is less problematic to determine MAC in pregnant women undergoing termination of pregnancy, however, and therefore we compared the MAC of isoflurane in these women with the MAC in matched nonpregnant women. METHODS: Patients underwent inhalational induction of anesthesia with isoflurane and tracheal intubation. MAC was determined in each patient by testing the response to a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical stimulus to the ulnar nerve at varying concentrations of isoflurane. The end-tidal concentration of isoflurane was kept constant for 10 min before each stimulus and the concentration of isoflurane ultimately varied in steps of 0.05% until we obtained a sequence of three alternate responses (move, not move, move) or (not move, move, not move). MAC for each patient was taken as the mean of the two concentrations just permitting and just preventing movement. MAC for the group was taken as the median of the individual MAC values. A blood sample was taken immediately before induction of anesthesia for measurement of progesterone concentrations. Data were compared between groups by the Mann-Whitney test. RESULTS: The median (range) MAC for isoflurane in the pregnant group, 0.775% (0.675-0.825), was less than that in the nonpregnant group, 1.075% (1.025-1.175) (P < 0.001). The median (range) plasma progesterone concentration in the pregnant group, 63.4 (0.8-106) nM, was greater than that in the nonpregnant group, 8.4 (0.7-66) nM (P < 0.02). CONCLUSIONS: The MAC of isoflurane was reduced by 28% in pregnant women at 8-12 weeks' gestation compared with that of nonpregnant controls.


Chan M,Mainland P, Gin TMinimum Alveolar Concentration of Halothane and

Enflurane Are Decreased in Early Pregnancy Anesthesiology85:782-6, 1996

� The MAC of halothane and enflurane were compared in pregnant women undergoing elective termination of pregnancy and in nonpregnant women.

� Methods: We studied 16 pregnant women scheduled for termination of pregnancy at 8 to 13 weeks gestation and 16 nonpregnant patients undergoing laparoscopic sterilization. Eight patients in each group received halothane and the others received enflurane. After inhalational induction of anesthesia and tracheal intubation, MAC was determined in each patient by observing the motor response to a 10-s, 50-Hz, 80-mA transcutaneous electric tetanic stimulus to the ulnar nerve at varying concentrations of either halothane or enflurane. The end-tidal concentration of inhalational anesthetic was kept constant for at least 15 min before each stimulus and the concentration was varied ultimately in steps of 0.05 vol% (halothane) or 0.10 vol% (enflurane) until a sequence of three alternate responses (move, not move, move) or (not move, move, not move) was obtained. Minimum alveolar concentration for each person was taken as the mean of the two concentrations just permitting and just preventing movement, and MAC for the group was the median of individual MAC values. Confidence intervals were calculated for the percentage decrease in MAC for pregnant women compared with nonpregnant women.

� Results: The median (range) MAC of halothane, 0.58 vol% (0.53 to 0.58), and enflurane, 1.15 vol% (0.95—1.25), in the pregnant women were less than those in the nonpregnant women, 0.75 vol% (0.70 to 0.78), P = 0.0005 and 1.65 vol% (1.45 to 1.75), P = 0.0007, respectively. The percentage decrease (95% CI) in MAC for pregnant women was 27% (20 to 27%) for halothane and 30% (24 to 36%) for enflurane.

� Conclusions: The MAC of halothane and enflurane were reduced by a similar degree in pregnant women at 8 to 13 weeks gestation compared with nonpregnant women.


Cameron CB, Gregory GA, Rudolph AM, Heymann M: The cardiovascular and metabolic effects of halothane in normoxic

and hypoxic newborn lambs. ANESTHESIOLOGY 62:732-7, 1985

� Oxygen consumption, cardiac output, and tissue oxygen delivery were measured in normoxic and hypoxic 1-3-day-old lambs during the following six conditions: 1) (control) paralysis with pancuronium and controlled ventilation with room air; 2) paralysis, controlled ventilation and hypoxia (PaO2 = 30 +/- 3 mmHg, [SD]); 3) paralysis, controlled ventilation with room air and 0.5 MAC halothane; 4) paralysis, controlled ventilation, hypoxia, and 0.5 MAC halothane; 5) paralysis, controlled ventilation with room air, and 1 MAC halothane; and 6) paralysis, controlled ventilation, hypoxia, and 1 MAC halothane. During normoxia, 0.5 and 1 MAC halothane decreased total body oxygen consumption, cardiac output, and arterial blood pressure. One-half MAC halothane had no effect on blood flow to any organ except muscle, whose flow decreased 64%. One MAC halothane decreased blood flow to the brain, heart, kidney, muscle, and gut. Both concentrations of halothane decreased serum catecholamine levels below control values and prevented hypoxia from increasing catecholamine levels. Hypoxia decreased the oxygen consumption about 40% from the immediately previous normoxic value, whether the animals were anesthetized or not. Tissue oxygen delivery followed changes in blood flow. The cardiac output, arterial blood pressure, and heart rate of anesthetized, hypoxic animals were not different from those in the previous normoxic condition. Halothane did not prevent redistribution of blood flow to the heart and brain of hypoxic animals, nor did halothane prevent hypoxic pulmonary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS).


Effects of halothane anesthesia 0.5 & 1 Mac in normoxic and hypoxic lambs (Cameron

et al. The cardiovascular and metabolic effects of halothane in normoxic and hypoxic newborn lambs.

ANESTHESIOLOGY 62:732-7, 1985)

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