bouee;3518047 said:
Hi everyone,
I have a problem, and I hope you can help, especially those with medical or pharmaceutical knowledge :
I have been thinking about Chernoffs cross the whole week end, and why they don't want to admit there was a drip, want to say that Alberto lied about the slit bag with the bottle on the IV pole, and what Dr White is going to say..
I don't think White is going to contradict anything Dr Shafer says, that would be stupid. As I said in a previous post, when Chernoff was asking about all the studies Dr White and Dr Shafer did together, it sounded, at least to me, like Dr Shafer was the one who did the modelling and calculations, and so Dr White was the one who was studying the drugs and it effects.
So the defense goes crazy when anyone mentions a drip, or anything about the tube that, maybe, well to me it's likely, was in Murray's pockets when he arrived at UCLA. They definitely want an injection theory, even though the self injection theory would be a lot more credible with a tube, Michael only had to unclamp it. Especially since according to Murray, Michael was "legally blind" (look at the size of the injection port, it's really small), and somehow he didn't leave any fingerprints on the bottle and the syringe, in spite of all he had to do to draw propofol out of the bottle (push and pull the plunger at least twice, and hold the bottle)
Dr Shafer based everthing on apnea, resiratory arrest , and the delay bewteen respiratory and cardiac arrest. So the only way out of this, for Dr White, would be to say that Michael went directly into cardiac arrest, or in less than the 2 or 3mns needed for concentration to drop enough according to Dr Shafer's calculations (the graphs with the injection simulations on day 14). This is basically what Soundmind has been saying, and that explains why the defense needs Murray away from the room more than 2 mn.
I looked at the autopsy report, anesthesiology consult, Dr Calmes talks about "respiratory depression" and "cardiovascular depression" and it sounded like 2 different things sometimes, and she mentions that a bolus injection should not be too fast.
So my question is : what is a cardiovascular depression, how fast can it be, can propofol send you directly into cardiac arrest , without a respiratory depression first ??
They are many problems with the cardiac arrest theory though : none of the doctors who have testified so far have mentionned it (Drs Steinberg, Kamangar, Shafer), they all said the risk was apnea, and Dr Shafer in an anesthesiogist. That's my major problem, how can 3 doctors overlook this ? But they all said you need to monitor the heart and BP.
Then how does the pulse that Murray said he felt would fit into this ? I wouldn't be surprised if the defense is prepared to call their client a liar again, But thats a big big lie or several lies at least (he "witnessed" the arrest, felt the pulse). It would make not calling 911 right away look worse. Why didn't Murrat plead guilty, I don't understand it either.
That wouldn't change anything about the verdict, there are tons of other things to convict the defense can't do anything about.
What I'm worried about is that the self injection theory would remain in some people's minds, even though it's not credible for the other reasons that I mentionned, and I don't want that to happen.
Uuugh my head hurts...
i hope this helps (sorry this is going to be long, I'd rather not interpret the text so I will just copy)... it's from Miller's Anesthesia, 7th edition... the major cardio
vascular effect is a drop in blood pressure, and if you have pre-existing cardiac problems, this can lead to bad stuff. there's also a decrease in cardiac ouput (the amount of blood the heart pumps each minute), seemingly by decreasing the strength with which the heart muscle is beating:
"Effects on the Cardiovascular System
The cardiovascular effects of propofol have been evaluated after its use for induction and for maintenance of anesthesia (
Table 26-2).
[SUP][108][/SUP] The most prominent effect of propofol is a decrease in arterial blood pressure during induction of anesthesia. Independent of the presence of cardiovascular disease, an induction dose of 2 to 2.5 mg/kg produces a 25% to 40% reduction of systolic blood pressure.
[SUP][108,112,113][/SUP] Similar changes are seen in mean and diastolic blood pressure. The decrease in arterial pressure is associated with a decrease in cardiac output/cardiac index (?15%),
[SUP][112,113][/SUP] stroke volume index (?20%),
[SUP][113][/SUP] and systemic vascular resistance (15% to 25%).
[SUP][112][/SUP] Left ventricular stroke work index also is decreased (?30%). When looking specifically at right ventricular function, propofol produces a marked reduction in the slope of the right ventricular end-systolic pressure-volume relationship.
[SUP][114][/SUP]
Table 26-2 -- Hemodynamic Changes after Induction of Anesthesia with Nonbarbiturate Hypnotics
| | | | | | | |
| HR | −9 ? 13% | Unchanged | −5 ? 10% | 0-59% | Unchanged | −14 ? 12% | −10 ? 10% |
| MBP | 0-19% | 0-10% | 0-17% | 0 ? 40% | −7-20% | −12-26% | −10-40% |
| SVR | −22 ? 13% | −5-15% | −10 ? 14% | 0 ? 33% | −10-35% | 0-20% | −15-25% |
| PAP | 0-10% | Unchanged | −9 ? 8% | +44 ? 47% | — | Unchanged | 0-10% |
| PVR | 0-19% | Unchanged | −18 ? 6% | 0 ? 33% | Unchanged | Unchanged | 0-10% |
| PAO | Unchanged | +25 ? 50% | Unchanged | Unchanged | — | 0-25% | Unchanged |
| RAP | Unchanged | Unchanged | Unchanged | +15 ? 33% | Unchanged | Unchanged | 0-10% |
| CI | Unchanged | Unchanged | −20 ? 14% | 0 ? 42% | 0 ? 16% | 0-25% | −10-30% |
| SV | 0-−8% | 0-10% | 0-20% | 0-21% | Unchanged | 0-18% | −10-25% |
| LVSWI | 0-36% | Unchanged | 0-33% | 0 ? 27% | — | −28-42% | −10-20% |
| dP/dt | Unchanged | — | 0-18% | Unchanged | — | 0-12% | Decreased |
<thead>
<th align="left"> </th><th align="left">Diazepam</th><th align="left">Droperidol</th><th align="left">Etomidate
*
</th><th align="left">Ketamine</th><th align="left">Lorazepam</th><th align="left">Midazolam</th><th align="left">Propofol</th>
</thead><tbody>
</tbody>
CI, cardiac index; dP/dt, first derivative of pressure measured over time; HR, heart rate; LVSWI, left ventricular stroke work index; MBP, mean blood pressure; PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; PAO, pulmonary artery occluded pressures; RAP, right atrial pressure; SV, stroke volume; SVR, systemic vascular resistance.
|
<tbody id="legend">
</tbody>
| [SUP]*[/SUP] | The larger deviations are in patients with valvular disease. |
<tbody>
</tbody>
In patients with valvular heart disease, pulmonary artery and pulmonary capillary wedge pressure also are reduced, a finding that implies the resultant decrease in pressure is due to a decrease in preload and afterload. Although the decrease in systemic pressure after an induction dose of propofol is due to vasodilation, the direct myocardial depressant effects of propofol are more controversial. The decrease in cardiac output after propofol administration may be via its action on sympathetic drive to the heart. Propofol at high concentrations (10 ?g/mL) abolishes the inotropic effect of α but not β adrenoreceptor stimulation, and enhances the lusitropic (relaxation) effect of β stimulation.
[SUP][115][/SUP] Clinically, the myocardial depressant effect and the vasodilation seem to be dose-dependent and plasma concentration–dependent.
[SUP][116][/SUP] The vasodilatory effect of propofol seems to be due to a reduction in sympathetic activity,
[SUP][117][/SUP] a direct effect on intracellular smooth muscle calcium mobilization,
[SUP][118][/SUP] inhibition of prostacyclin synthesis in endothelial cells,
[SUP][119][/SUP] reduction in angiotensin II–elicited calcium entry,
[SUP][120][/SUP] activation of K[SUP]+[/SUP] adenosine triphosphate channels, and stimulation of nitric oxide. The stimulation of nitric oxide may be modulated by intralipid rather than propofol.
[SUP][121][/SUP]
Heart rate does not change significantly after an induction dose of propofol. Propofol either may reset or may inhibit the baroreflex, reducing the tachycardic response to hypotension.
[SUP][122][/SUP] Propofol also decreases cardiac parasympathetic tone in a dose-dependent manner.
[SUP][123][/SUP] Propofol has a minimal direct effect on sinoatrial node function or on normal atrioventricular and accessory pathway conduction.
[SUP][124][/SUP] Propofol attenuates the heart rate response to atropine in a dose-dependent manner. During an infusion of 10 mg/kg/hr of propofol, a cumulative dose of atropine of 30 ?g/kg increased heart rate greater than 20 beats/min in only 20% of subjects compared with 100% in the absence of propofol.
[SUP][125][/SUP] Propofol suppresses atrial (supraventricular) tachycardias and probably should be avoided during electrophysiologic studies.
[SUP][126][/SUP]
In retrospective review of 2406 patients, Reich and colleagues
[SUP][127][/SUP] showed that 9% of patients experienced severe hypotension 0 to 10 minutes after induction of general anesthesia. Statistically significant multivariate predictors of hypotension 0 to 10 minutes after anesthetic induction included American Society of Anesthesiologists (ASA) class III through V, baseline mean arterial pressure (MAP) less than 70 mm Hg, age 50 years or older, use of propofol for induction of anesthesia, and increasing induction dosage of fentanyl. The combination of propofol with fentanyl was a particularly potent stimulus for hypotension. A prolonged postoperative stay or death was more common in patients with versus patients without postinduction hypotension; however, the use of propofol per se was not associated with increased morbidity.
[SUP][127][/SUP] Limited data indicate that 0.5 mg/kg of ketamine is able to better prevent decreases in hemodynamics after a propofol induction alone or in combination with fentanyl (1 ?g/kg).
[SUP][128][/SUP]
During maintenance of anesthesia with a propofol infusion, arterial systolic blood pressure also is decreased to 20% to 30% less than preinduction of anesthesia levels. In patients allowed to breathe room air during a maintenance infusion of 100 ?g/kg/min of propofol, there is a significant decrease in systemic vascular resistance (30%), but cardiac index and stroke index are unaltered. In contrast, in patients receiving a narcotic premedication and nitrous oxide with an infusion of propofol (54 ?g/kg/min and 108 ?g/kg/min) for maintenance during surgery, systemic vascular resistance is not significantly decreased from baseline, but cardiac output and stroke volume are decreased. This situation is probably explained by the observation that propofol infusions produce a dose-dependent decrease of sympathetic nerve activity, attenuating the reflex responses to hypotension. In the presence of hypercarbia, the reflex sympathetic responses are better maintained.
[SUP][129][/SUP]
Increasing the infusion rate of propofol from 54 to 108 ?g/kg/min (blood concentration 2.1 to 4.2 ?g/mL) produces only a slightly greater decrease in arterial blood pressure (−10%). The peak plasma concentrations obtained after a bolus dose are substantially higher than the concentrations seen with a continuous infusion. Because the vasodilatory and myocardial depressant effects are concentration-dependent, the decrease in arterial blood pressure from propofol during the infusion phase (maintenance of anesthesia) is much less than that seen after an induction of anesthesia bolus. When propofol was compared with midazolam for sedation after coronary revascularization, propofol resulted in a 17% less frequent incidence of tachycardia, a 28% less frequent incidence of hypertension, and a 17% more frequent incidence in hypotension. These differences in hemodynamic variables resulted in no difference in the number or severity of ischemic events between the two groups. An infusion of propofol results in a significant reduction in myocardial blood flow and myocardial oxygen consumption,
[SUP][108,111][/SUP] a finding that suggests that the global myocardial oxygen supply-to-demand ratio is preserved.
The cardioprotective effect of propofol versus volatile anesthetics in patients having cardiac surgery on or off cardiopulmonary bypass is less debatable. In two large studies comparing propofol with sevoflurane in patients undergoing cardiac surgery, postoperative troponin were lower and hemodynamic function better in patients receiving sevoflurane.
[SUP][130,131][/SUP] A study comparing desflurane with propofol in patients undergoing off-pump coronary artery bypass showed similar results.
[SUP][132][/SUP] In contrast, a small study that administered high-dose propofol (120 ?g/kg/min), low-dose propofol (60 ?g/kg/min) while on pump, or titrated isoflurane throughout surgery showed improved troponin levels and better hemodynamic function in the large-dose propofol group compared to the isoflurane or low-dose propofol group.
[SUP][133][/SUP] This study may indicate that cardioprotection with propofol is dose dependent, but needs confirmation.
Heart rate may increase,
[SUP][111][/SUP] decrease,
[SUP][110][/SUP] or remain unchanged
[SUP][109][/SUP] when anesthesia is maintained with propofol. The extent of hypotension, the ability for the patient to compensate, and the use of any other concomitant drugs are likely the most important factors in determining what happens to the heart rate after propofol administration."
So I guess if they say hypotension caused his heart to stop beating?? I don't know if that's possible... and they still have the problem of Murray's feeling a thready pulse of 122... I guess we will find this week where they're going with this =/
