Prognosis An isoelectric EEG is one of the additional tests suggested in the USA for con \201 rmation of brain death. The EEG has This page intentionally left blank 138 A EYNON Other forms of neurological monitoring Tissue metabolism Brain tissue oxygenation The Licox monitor (GMS, Kiel-Mielkendorf, German y) allows measurement of brain tissue oxygenation that can be used in conjunction with othe r monitoring modalities to measure the adequacy of cerebral perfusion. The probe is inserte d either via a single-lumen bolt, or via a triple-lumen bolt with both an ICP monitor and a microdialysis catheter. Oxygen diffuses from the tissue into an inner electrolyte chamber in the catheter which generates an electric current using a polarographic electrochemical s ensor. The probe measures tissue oxygenation from an area of 15mm3 around the tip. The ris ks of infection and signi \201 cant haemor- rhage associated with the technique are low. N ormal brain tissue oxygen values range from 25 to 30mm Hg. Levels <20mm Hg have been report ed following head injury and levels <5mm Hg are associated with increased mortality. Improv ements in mortality and functional outcome have been reported in patients treated with ther apy aimed at maintaining a brain tissue oxygen level >25mm Hg compared with patients treate d with a tradi- tional ICP/CPP-guided therapy. (primarily iron in oxyhaemoglobin and deoxyhaemoglobin, and copper in cytochrome AA3). Chan ges in the concen- tration of near-infrared light as it passes through these compounds can be measured, and this allows calculation of the oxidation status. Generally, optodes are pl aced 4 \200\2237cm apart on the scalp. Light waves of 700 \200\2231000nm can penetrate the scalp, skull and brain to a depth of a few centimeters, allowing illumi- nation of a volume of 10ml of brain. Normal values of oxygenated hemoglobin are 60 \200\22380%. NIRS has bee n used to monitor patients with brain injury or intracranial haem- orrhage, and patients un dergoing carotid endarterectomy. The major limitation to its use is the dif \201 culty in distin- guishing intracerebral and extracerebral tissues. NIRS is able to follow trends in oxygenation in individual patients. Laser Doppler \202 owmetry Doppler change of laser light can be used to measure movement of red cells within the brain microcirculation. A small Doppler probe is placed within the brain tissue itself. It can obviously only measure CBF within a small area of brain tissue. It has been used experimentally to assess therapeutic interventions, to detect ischaemia a nd to assess CO2 reactivity and autoregulation following head injury. Microdialysis Microdialysis involves placement of a \201 ne catheter into the brain paren chyma. Dialysis \202 uid is continuously perfused through the catheterm which is lined wi th a dialysis mem- brane, typically with a molecular weight cut-off of 20kDa. Low molecula r weight substances cross the membrane and their concentrations can be measured in the dial ysate. Unless there is total equilibration, the concentration of molecules in the dialysate will be lower than that in the extracellular \202 uid. The proportion of molecule recov- ered depends on the membrane size, membrane area, diffusion speed of the molecule and the rate of \202 ow of the dialysate. Glucose, lactate, glutamate, glycerol and the lactate/p yruvate ratio have all been used as markers of cerebral metabolism. Larger membrane sizes a llow measurement of polypep- tides and cytokines that may be implicated in the damage or re pair processes. A recent consensus statement sug- gests that catheters should be placed in the right frontal region in patients with diffuse head injury, in the area of brain at risk in patients with subarachnoid hemorrhage, and in the penumbral area and a second catheter in normal brain in patients with focal lesions. The lactate/pyruvate and lactate/glucose ra tios are sensitive markers of tissue hypoxia/ischaemia. A high lactate/pyruvate ratio corre lates with the severity of injury and outcome in head injury. Alterations in these levels m ay precede eleva- tions in ICP in acute brain injury, allowing earlier interven- tion. Simi lar changes have been seen before development of delayed ischaemic de \201 cits due to cer ebral vasospasm in subarachnoid hemorrhage. High levels of the excitatory amino acids gluta mate and aspartate have been found in areas of contusion or secondary ischaemic injury. Thermal diffusion \202 owmetry The thermal conductivity of brain tissue varies in propor- tion to CBF. Two thermistors can be placed on the brain surface, and blood \202 ow calcu lated by means of heating one plate and measuring the thermal difference between plates. Ag ain only a small amount of brain tissue can be assessed. Peripheral nerve and muscle electrophysiology Sensory evoked potentials (SEPs) These are th e electrical response of the cortex, brainstem and spinal cord to a peripheral sensory stim ulus. They can be recorded in response to stimulation of any sensory nerve, whether cranial or peripheral. The most commonly evoked SEPs are somatosensory (SSEP), visual (VEP) and br ainstem auditory (BAEPs). SSEPs are recorded commonly from the median, ulnar and posterior tibial nerves. SSEPs are a useful method of predicting outcome in post-traumatic and anoxic coma patients. Bilaterally absent SSEPs are strongly associated with poor outcome. SSEPs m ay also be used in surgery on the spinal column, carotid endarterectomy and cerebral aneury sm surgery. VEPs are measured in response to a visual stimulus (usually a flashing light or reversing checkerboard). VEPs are profoundly affected by anesthesia and are occasionally u sed to assess optic nerve function in pituitary surgery of surgery on the anterior cranial fossa. BAEPs are used in acoustic neuroma surgery where they have been shown to be useful i n preserving the function of the auditory nerve. They may also be used for monitoring durin g posterior fossa surgery. Nerve conduction studies These can be used to diagnose and classify generalized neuropathie s that may be seen on the ICU. A stimulus is applied to a nerve at two points along its cou rse, and the response recorded. In axonal neuropathies, the amplitude Cerebral blood \202 ow and metabolism NIRS Near-infrared spectroscopy (NIRS) measures reg ional cerebral oxygen saturation by measuring near-infrared light reflected from the chromo phobes in the brain 139 CHAPTER 8.4 Other forms of neurological monitoring Table 8.4.1 Nerve conduction studiy patterns in common clinical conditions Motor nerve conduction Sensory nerve conduction EMG Slowed or blocked Reduced amplitude Reduced and falls further with repetition Reduced or absent Normal Normal Later denervation Denervation widespread Increased jitter on single \201 bre testing Guillain \200\223Barr syndrome Motor neuron disease Myasthenia gravis Reduced Reduced Fibrillations Critical care polyneuropathy Further reading Bhatia A, Gupta AK. Neuromonitoring in the intensive care unit. 1. Intracra nial pressure and cerebral blood \202 ow monitoring. Intensive Care Med 2007; 33: 1263 \200\22371. of the response will fall but conduction velocity is well preserved. In contrast, in demyel inating neuropathies, although the amplitude may fall, the conduction velocity is also redu ced (Table 8.4.1). Critical illness polyneuropathy is a diffuse axonal neuropathy usually s een in patients with severe sepsis and multi-organ failure. It is usually consid- ered when the patient fails to wean from ventilation and remains profoundly weak. Patients have musc le wasting that often spares the face (although there may be evidence of facial involvement on electrophysiological testing). Bhatia A, Gupta AK. Neuromonitoring in the intensive care unit. 2. Cerebral oxygenation mon itoring and microdialysis. Intensive Care Med 2007; 33: 1322 \200\2238. Stieffel MF, Spiotta A, Gracias VH, et al. Reduced mortality rate in patients with severe t raumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg 2005; 103: 8 05 \200\22311. Electromyography (EMG) This examines the electrical activity of a speci \201 c muscle. A n eedle electrode is placed into the muscle, and the spon- taneous activity of the muscle is recorded. EMG may help in the diagnosis of motor neuron disease, peripheral nerve root and plexus injuries, and myopathies (Table 8.4.1). This page intentionally left blank 141 Chapter 9 Fluids Chapter contents Crystalloids 142 Colloids 144 Sodium bicarbonate 146 Blood 150 142 M KUPER Crystalloids De \201 nition A substance with properties of a crystal; aqueous \202 uids containing di ssolved sugars or salts (Table 9.1.1). Outcome in critical care patients resuscitated with saline is as good as with albumin Hartm ann \200\231s avoids hyperchloraemic metabolic acidosis, due to lower chloride and because lactate metabolism consumes hydrogen ions. However outcome bene \201 t not yet demonstrate d, Classi \201 cation \200 Isotonic crystalloids \200 \200\230Normal saline \200\231 \200 Hartmann \200\231s (Rin ger \200\231s lactate) Hypotonic crystalloids \200 \200\230Half-normal saline \200\231 \200 \200\230Dextrosaline \200\231 \200 5% Dextrose \200 50% Dextrose Hypertonic crys talloids. \200 Hypertonic saline Hypotonic crystalloids Although initially iso- or hyperosmolar, glucose-containing solution s are rendered hypotonic by cellular uptake and metabolism of glucose. Pharmacokinetics \200 Tonicity is the effective osmolality with respect to the cell membrane. Hypotonic solutions behave like a water load and distribute through the intravascular, interstitial and intrac ellular volumes Half-normal saline distributes half extracellularly like saline and half th rough the body water. Isotonic crystalloids In the 1880s Ringer found that a \200\230balanced \200\231 \202 ui d more like plasma retained isolated organ function better than \200\230nor- mal \200\231 saline. Hartmann added lactate in the 1930s. Pros \200 Allow glucose provision, in diabetics and critical care patients not established on nutriti on Allow supply of IV hydration since intravenous water is hypoosmolar so causes haemolysis . Pharmacokinetics \200 \200 Isotonic so do not lose or gain water by osmosis Distribute through the extracellular volum e, because sodium is con \201 ned extracellularly by cell membrane NaKATPase activity Intr avascular retention is greater in hypovolaemia The plasma volume of 3l is one- \201 fth of the extracellular volume of 15l, so by 1h 20% remains intravascularly, i.e. 200ml/l Norma l saline: after rapid infusion of 2l, 24% remains intravascularly at 1h, 22% by 6h (56% rem ains in the body) Hartmanns: 18% remains intravascularly at 1h, 14% by 6h (30% remains in t he body). More rapid diuresis may be due to mild hypotonicity, inhibiting antidiurectic hor - mone (ADH), or to lower chloride, reducing renal vaso- constriction, Cons \200 Hypotonic so inappropriate for resuscitation of \202 uid de \201 cits ADH secretion incr eases in response to non-osmotic factors including surgery, infection and pain. The result- ing retention of water over sodium, in conjunction with \200\230maintenance \200\231 hypo tonic IV fluid, can cause severe hyponatraemia leading to seizures and death 10% dextrose n eeds a large free \202 owing vein, and con- tinuous infusion of 50% dextrose needs centra l access to avoid thrombophlebitis Rapid infusion causes hyperglycaemia, glycosuria and osm otic diuresis Concurrent \200\230sliding scale \200\231 insulin administration is often ne cessary to maintain glycaemic control. \200 Pros \200 \200 No anaphylactoid reactions Saline produces a more sustained volume effect than Hartmann \200\231s Lactate in Hartmann \200\231s is metabolized via pyruvate, to glucose in the live r, or to carbon dioxide and water in peripheral tissues. One liter provides 9kcal. Both are cheap, Role \200 Dextrosaline usage recently restricted in children because of deaths due to hyponatraemia H alf-normal saline considered safe for \202 uid mainten- ance in stable children, although isotonic solutions were recommended if potential water retention, e.g. hypotension, hypovo laemia, perioperative care, sepsis, diarrhea 50% dextrose is used in the emergency treatmen t of hypoglycaemia and is given with insulin in acute manage- ment of dangerous hyperkalaem ia To supply water over and above saline, e.g. given a supranormal serum sodium. However, i n children, cor- rect signi \201 cant hypernatraemia >160mmol/l slowly with isotonic cryst alloid More concentrated dextrose solutions reduce the asso- ciated water load and are usef ul for administration alongside isotonic crystalloid maintenance. For instance, 10 \200\223 20ml/h of 50% dextrose provides 17 \200\22334kcal/h. However, central venous access is requ ired to avoid thrombophlebitis. Cons Rapid administration of large volumes can cause: \200 \200 Dilutional procoagulant effect Saline produces a hyperchloraemic metabolic acidosis, of unc ertain clinical significance; caused either by decreased strong ion difference due to hyper chloraemia or by dilution of bicarbonate Saline (but not Hartmann \200\231s) produced abdom inal dis- comfort and subtle cognitive de \201 cits, Roles \200 Appropriate for both \202 uid resuscitation and mainte- nance \202 uid administration 143 CHAPTER 9.1 Crystalloids Table 9.1.1 Crystalloid composition Na+ mEql/l K+ mEql/l Cl \200\223 mEql/l Ca2+ mEql/l Fluid Other names Glucose mEql/l kcal/l Lactate mEql/l Calculated osmolarity mOsm/l Tonicity Sodium chloride 0.9% Normal saline 154 \200\223 154 \200\223 \200\223 \200\223 \200\223 308 Isotonic Ringer \200\231s solution \200\223 147 4 2.2 \200\223 \200\223 \200\223 Ringer \200\231s lactate Hartmann \200\231s solution 130 4 110 2 \200\223 \200\223 28 275 Isotonic 77 \200\223 77 \200\223 111 85 \200\223 265 Hypotonic Half \200\223normal saline + dextrose Sodium chloride 0.45% + Dextrose 2% Dextrose saline 31 \200\223 31 \200\223 222 136 \200\223 262 Hypotonic Sodium chloride 0.18% + dextrose 4% 5% Dextrose \200\223 \200\223 \200\223 \200\223 \200\223 278 170 \200\223 278 Hypotonic 10% Dextrose \200\223 \200\223 \200\223 \200\223 \200\223 556 340 \200\223 556 Hypotonic 50% Dextrose \200\223 \200\223 \200\223 \200\223 \200\223 2778 1700 \200\223 2778 Hypotonic \200\223 Sodium chloride 7.5% Hypertonic saline 1283 \200\223 1283 \200\223 \200\223 \200\223 2567 Hypertonic Plasma \200\223 144 5 107 2.3 5 \200\223 <1 290 Isotonic \200 \200 Hypertonic crystalloids Hypertonic saline Hypertonic solutions from 1.8 to 7.5% saline have been employed, either alone or with colloid. Hypertonic 7.5% saline acutely increases intr avascular volume by 4 \200\22310 times the infused volume, by drawing interstitial and intr acellular water into the intravascular space. The salt and water then redistribute through the extracellular volume, over about an hour. Combination of 7.5% saline with either dextra n 70 or hetastarch prolongs intravascular retention. Theoretical risk of central pontine myelinosis Potential for rebound intracranial hypertens ion Potential for coagulopathy. Role \200 Amall volumes, so advocated for battle \201 eld resuscita- tion In burns, produce less ris e in intra-abdominal pressure than Hartmann \200\231s Improved outcome in penetrating traum a Reduce cerebral swelling and ICP in traumatic brain injury, but no outcome bene \201 t f ound. \200 Pros \200 \200 \200 Increased intravascular volume Haemodilution with reduced viscosity cf starches Vasodilatio n, with reduced afterload and cardiac work, and perhaps improved regional blood \202 ow E ndothelial \200\230deswelling \200\231 due to osmotic effect may improve capillary blood \202 ow Small resuscitation volumes; 250ml of 7.5% hypertonic saline is an effective initi al resuscitation \202 uid. Improved microcirculation with splanchnic vasodilata- tion. Further reading Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for \202 uid resuscitation in the intensive care unit. N Engl J Med 2004; 350: 2247 \200\223 56. Kuper M, Soni N. Fluids and electrolytes. In: Webster NR, Galley NF, eds. Anesthesia science. Oxford: Blackwell, 2006: 198 \200\223200. National Patient Safety Agency. Patient Safety Alert No 22. Reducing the risk of hyponatrae mia when administering intravenous infu- sions to children. 2007. Oda J, Yamashita, K, Inoue T, et al. Hypertonic lactated saline resus- citation reduces the risk of abdominal compartment syndrome in severely burned patients. J Trauma 2006; 60: 64 \200\22371. Cons \200 \200 Severe hypernatraemia Hyperoncotic plasma Wilkes NJ. Hartmann \200\231s solution and Ringer \200\231s lactate: targeting the fourth space. Clin Sci (Lond) 2003; 104: 25 \200\2236. 144 M KUPER Colloids \200 De \201 nition A colloidal \202 uid is a dispersion of small particles in a con- tinuous \202 uid phase, which exert an osmotic effect because the endothelium is relatively impe rmeable to the colloid particles. \200 Initial 80% volume effect. \200\223ve charge of gelofusin repels the endothelium, extend- ing plasma half-life. Pros \200 \200 \200 \200 \200 \200 \200 Initially effective volume expansion Near complete renal clearance Cheap Minimal coagulopat hy No renal impairment Rapid near complete excretion No itch. Human plasma derivatives \200 Semi-synthetic colloids \200 \200 \200 Human albumin solution Gelatins Dextrans Starches The ideal colloid has yet to be found, e.g. all colloids can cause anaphylactoid reactions, of which 20% are severe. Consult manufacturer \200\231s data sheets for maximum doses. Hyp ertonic electrolyte carrier solutions are discussed in the previous chapter. Cons \200 \200 \200 Only 20% remains intravascularly at 90 min Highest rate of anaphylactoid reactions Bovine o rigin so possible religious objections, and risk of nv-CJD transmission cannot be excluded Calcium in Haemaccel can coagulate transfused blood. Human plasma derivatives Human albumin solution (HAS) Constituents and volume effect \200 \200 Role \200 \200 \200 Most commonly used colloid in the UK Good side effect pro \201 le except anaphylactoid rea ctions Suitable for short-lived plasma expansion, e.g. during regional or general anesthesi a. Derived from plasma from thousands of donors. 4.5% HAS is iso-oncotic, whereas 20% HAS is h yperon- cotic but \200\230salt-poor \200\231 so mildly hypotonic, so will draw \202 uid intravascularly Initial volume effect is the intravascular volume expan- sion as a percenta ge of the \202 uid volume given. \200 20% leaves the plasma in health 32% leaves in sep sis, due to leaky capillaries. Dextrans Constituents and volume effect \200 Four hours after administration of 20% HAS: Glucose polymers produced by Leuconostac bacteria grown in sucrose. Iso-oncotic dextran 70 has less initial volume effect than dextran 40, which is hyperoncotic Volume effect is rela tively prolonged as there is no intra- vascular metabolism; large molecules are hydrolysed by tissue dextran-1,6-glucosidase and small molecules are renally \201 ltered. \200 Pros \200 \200 \200 \200 \200 Anaphylactoid reactions are very rare +ve charge binds drugs, toxins and free radicals Anti oxidant capacity, clinical relevance unclear No itch No renal dysfunction. Pros \200 Better intravascular persistence than gelatins. Cons \200 \200 Cons \200 Expensive Cannot exclude transmission of infections, e.g. new vari- ant Creutzfeld \200\223 Jacob disease (nv-CJD). Coagulopathy, with reduced factors VII and VIII and von Willebrand factor Intermediate risk of anaphylactoid reactions Erythrocyte aggregation with rouleaux formation inter- feres wi th cross-match Acute renal failure, attributed to increased urine viscos- ity and osmotic p ressure Half excreted unchanged, half oxidized over days. \200 Role \200 A suggestion from meta-analysis of increased mortality was refuted, but no outcome bene \201 t compared with saline was found in the SAFE study, even in patients with a low plasma albumin Possible bene \201 t in sepsis, following paracentesis and in diuretic-induced he patic encephalopathy Possibly harmful in traumatic brain injury \200\230Salt-poor \200\231 20% albumin requires less volume for a given increase in oncotic pressure; bene \201 t su ggested when given with furosemide in acute lung injury, though oxy- genation does not impr ove acutely. Role \200 \200 \200 Out of favor due to coagulopathy. Superseded by low molecular weight heparins for prophylax is against deep vein thrombosis Avoid in renal failure. Starches Constituents and volume effect \200 Semi-synthetic colloids Gelatins Constituents and volume effect \200 \200 \200 Derived from hydrolysed maize. Volume effect \200 Gelatins are derived from bovine collagen. Gelofusin is 4% succinylated gelatin. Haemaccel is urea-linked gelatin. Initial volume effect depends on number of osmotically active particles, and so on concentr ation 145 CHAPTER 9.2 Colloids Table 9.2.1 Characteristics of some starches Fluid Colloid MWw (kDa) MWn (kDa) Degree of substitution Plasma half-life (h) Initial volume effect (%) COP (mm Hg) Calculated osmolarity Albumin 4.5% Albumin 69 69 \200\223 16 100 25 300 Albumin 20% Albumin 69 69 \200\223 16 250 100 300 Dextran 40 10% Dextran 40 40 25 \200\223 4 200 >100 310 Dextran 70 6% Dextran 70 70 38 \200\223 6 140 75 309 Haes-steril 6% Pentastarch 200 60 0.5 12 100 34 310 Haes-steril 10% Pentastarch 200 60 0.5 12 145 80 308 Hespan 6% Hetastarch 450 70 0.7 24 100 27 310 Voluven Tetrastarch 130 60 0.4 3 100 36 309 Gelofusin Succinylated gelatin 30 22.6 \200\223 2 100 13 279 6% Dextran in 7.5% NaCl Dextran 70 70 38 \200\223 8 700 75 2567 Haemaccel polygeline 35 24.5 \200\223 2 100 13 300 MWw = weight average molecular weight; MWn = number average molecular weight; COP = colloid osmotic pressure. Table 9.2.2 The ideal colloid has yet to be found Fluid Volume ef \201 cacy Coagulopathy Anaphylactoid reaction rate Itch Renal impairment Infectious risk Cost Ideal \200 ++ \200\223 \200\223 \200\223 \200\223 \200\223 + Albumin ++ + 1 in 1010 \200\223 \200\223 + +++ Gelatin + ++ 1 in 290 \200\223 \200\223 + + HES ++ +++ 1 in 1724 ++ ++ \200\223 ++ Dextran ++ ++++ 1 in 366 \200\223 ++ \200\223 ++ Duration depends on metabolism, and on osmotically active metabolites seen, e.g. with Voluv en Metabolism slower with a high molecular weight, a high degree of hyroxyethyl substitutio n of glucose side chains and a high ratio of C2 compared with C6 substitution, Role \200 \200 \200 Effective and sustained volume effect Questions remain over side effects Avoid in renal fai lure, Balanced colloids \200 Pros \200 \200 \200 Starch in a more \200\230balanced \200\231 carrier solution (Hextend) containing glucose, lactate and a lower chloride avoids hyperchloraemic acidosis compared with starch in saline (Hetastarch). Less coagulopathy in vitro No outcome bene \201 t demonstrated yet. Lowest risk of anaphylactoid reactions Sustained volume effect Might reduce inflammation an d capillary leak, and improve microcirculatory perfusion. \200 Cons \200 \200 \200 Incomplete clearance from the body (50%) Incidence of itch up to 13% Coagulopathy, with red uced factor VIII and reduced von Willebrand activity. Increased bleeding in neurosurgery an d cardiac surgery, more marked with slowly degrad- able starches Renal impairment has been suggested with various starches, e.g. in the recent \200\230VISEP \200\231 trial Hyperamyl asaemia due to plasma amylase binding complicates the diagnosis of pancreatitis Hepatosplen omegaly and ascites in chronic dialysis patients Rapidly degraded starches with low molecul ar weight and low molar substitution, e.g. Voluven (HES 130/0.4) may avoid side effects. Further reading Kuper M, Gunning M P, Halder, S, et al. The short-term effect of hyperoncot ic albumin, given alone or with furosemide, on oxy- genation in sepsis-induced acute respir atory distress syndrome. Anesthesia 2007; 62: 259 \200\22363. Kuper M, Soni N. Fluids and electrolytes. In: Webster NR, Galley NF, eds. Anesthesia science. Oxford: Blackwell, 2006: 198 \200\223200. Wilkes N J, Woolf R, Mutch M, et al. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid \200\223base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 2001; 93: 811 \200\2236. 146 M PALAZZO Sodium bicarbonate When this formula is rewritten in the Henderson \200\223 Hasselbalch mode (to convert hydro gen ion concentration to its logarithmic representation pH) The body has developed an ef \201 cient system of buffers to minimize the life-threatening tendency to acidaemia and acidosis which follows normal metabolism. Stable blood pH is ess ential for ef \201 cient enzyme activity, and oxygen and carbon dioxide carriage by Hb. Th e body has four buffering conjugate pairs, Bicarbonate/carbonic acid \200\224the main extra cellular buffering system and the most important for \201 xed acids, while playing a majo r role in transportation of volatile acids to the lung. Tissue and plasma protein/hemoglobi n \200\224main intrac- ellular system accounting for 2/3 total body \200\231s buffering cap acity. \200\223) \200\224has plasma Phosphate system (HPO4 buffering capacity equivalent t o 20% that of bicarbonate but also active in the renal tubules. Ammonia/ammonium (NH3/NH4 \201 ned to the renal tubules. Classical acid \200\223base teaching is that the buffering systems do not operate in isolation but are in equilibrium with each other, the so-called i sohydric state. An acid load results in all buffers changing their equilibrium status. Buff ers are immediately effective but, once their capacity is exceeded, acidaemia results and a cidosis becomes revealed through clinical signs such as ventilatory stimulation, which incr eases CO2 removal in an attempt to restore near normal pH. The kidney further reduces acida emia by accelerating proton excretion; urine pH will fall to 5.5 in the absence of tubular dysfunction. This response is slower than the venti- latory change and reaches maximum ef \201 cacy after several hours. The isohydric behavior of buffers conveniently allows us to examine just one buffer system in order to assess body acid \200\223base status and predict changes under given loads. Carbonic acid dissociates poorly into the bicarbonate anion and a proton. However, carbonic acid very readily dissociates into dissolved carbon dioxide an d water. While carbonic acid is dif \201 cult to measure, dissolved carbon diox- ide can b e readily estimated and is directly proportional to carbonic acid: \200\223 ]/[CO2] pH = pK1 + log [HCO3 The dissolved carbon dioxide at body temperature can be calculated from the product of CO2 tension in plasma (40mm Hg (5.3kPa)) and the solubility coefficient (0.03mmol/l/mm Hg). Dis solved plasma CO2 is 1.2mmol/l \200\223 ] is 24mmol/l, so the (40 x 0.03). Normal plasma [ HCO3 \200\223 ]/[CO2] is 24/1.2 or 20. ratio [HCO3 The pK of the CO2/bicarbonate system is 6.1. If these values are substituted in the Henderson \200\223Hasselbalch equation pH = 6.1 + log 20 2 \200\223 and H2PO4 or pH = 6.1 + 1.3 = 7.4 (normal plasma pH) +) \200\224buffering is con- The relationship between the components of the Henderson \200\223Hasselbalch equation is th e basis of bicarbo- nate estimation from measured dissolved CO2 and pH from blood gas analy sis. Although the pK of carbonic acid is rather low at 6.1, resulting in a 20:1 ratio betwe en bicarbonate and carbon dioxide at physiological pH, thus making it seemingly less ef \201 cient than a buffer with pK 7.4 at normal pH, the car- bonic acid system becomes more ef \201 cient as pH falls. This is fortunate, since acidosis is the most common acid \200 \223base disorder. Furthermore, since it is the only system in which \200\223 ], and denom inator, [CO2], both the numerator, [HCO3 can be regulated by independent mechanisms, increa sed \201 xed acid loads are not only buffered by bicarbonate but also result in ventilato ry stimulation which reduces plasma CO2, facilitating the return towards normal pH. An alte rnative quantitative analysis of carbon dioxide and bicarbonate behavior has been proposed by Stewart. Acid \200\223base derangements and restoration by resuscitation, ventilation an d/or exogenous buffer administration is read- ily monitored through central venous or arter ial blood sampling. Persistent acid load from any cause may result in metabolic acidosis. I f the cause is due to excess organic acids such as lactate or ketoacids, successful managem ent of the cause progressively reduces production of acids, and the anions (lactate, acetoa cetate, -hydroxybutyrate) associated with the excess protons become metabolized to bicarb o- nate, therefore correcting acidosis without need for bicar- bonate. However, if the caus e is excess inorganic acids such as renal failure or renal tubular acidosis, or if reversi- bility of an organic cause is delayed by institutional proc- esses (wrong diagnosis, delay ed ischaemic bowel surgery), buffer base will become exhausted and supplementation required to increase stores or buy time while they are being regenerated. The homeostatic response to metabolic acidosis results in increased ventilation and CO2 removal in an attempt to mai ntain near normal pH. Failure to increase ventilation spontaneously or inadequate mechanica l ventilation to mimic hyperventilation will allow acidosis to deteriorate \200\223 H2O + CO2 = H2CO3 = H+ + HCO3 The relative plasma concentrations of H2CO3, dissolved CO2 and bicarbonate are 1:340:6800, respectively. H2CO3 is so small that it can be ignored, and the above equation rewritten as : \200\223 H2O + CO2 = H+ + HCO3 The law of mass action for the CO2/carbonic acid/bicarbo- nate buffer system becomes: \200\223 ]/[CO2][H2O] K = [H+] x [HCO3 Where K is a constant. [H2O] is also relatively constant and, by rearranging the equation, K[H2O] can be replaced by K1 \200\223 ]/[CO2] K1 = [H+] x [HCO3 147 CHAPTER 9.3 Sodium bicarbonate more rapidly. This is apparent from the Henderson \200\223 Hasselbalch equation. If pCO2 re mains unchanged, hydro- gen ion concentration will double for a 50% fall in bicarbonate con centration. The normal pCO2 response is a fall of 1.2mm Hg (0.16kPa) for a 1mmol/l fall in bicarbo- nate concentration. Therefore body weight kg x 1/5 x base de \201 cit = sodium bicarbo- nate (mmol) dose shoul d signi \201 cantly correct metabolic acidosis. In practice the dose is about twice this b ecause although bicarbonate is an extracellular buffer, it also facilitates the intracellul ar buffers to take up protons in accordance with the isohydric behavior of buffers. The fac ilitation of intracellular buffer activity effectively results in buffering capacity lost f rom the extracellular space for a given dose of bicarbonate. This in pharmacokinetic terms is an increase in bicarbonate vol- ume of distribution, although bicarbonate remains pre- d ominantly in the extracellular space. It is therefore common to see formulas suggesting dos es calculated on the basis of 1/3 to 1/2 body weight. However, in view of the potential for adverse effects on potassium and calcium concentrations if a full corrective dose is given , it is safer to give half the corrective dose to achieve pH 7.2 and reassess whether there is a clinical need for more. Common indications for sodium bicarbonate administration \200 Severe inorganic metabolic acidosis, pH <7.1 and when the precipitating pathophysiology is unlikely to reverse spontaneously, e.g. renal failure or sudden ischaemia of a major organ. Forced alkaline diuresis. Patients who develop meta- bolic acidosis following salicylate o verdose can bene \201 t from accelerated renal salicylate excretion by promoting an alkali ne diuresis. Typically 1l of isotonic (1.26%) sodium bicarbonate is given in the \201 rst hour, followed by 500ml of 5% dextrose, 500ml of saline and 500ml of 1.26% sodium bicarbon ate at hourly intervals. Ef \201 cacy of alkalinization is monitored by measuring urine pH , and dosing is altered to achieve values \211 7 and relating this to the need by observin g the fall in blood salicylate. Organic metabolic acidosis associated with hypopefu- sion w hether cardiogenic or hypovolaemic (blood loss or sepsis) in origin should be corrected wit h speci \201 c resuscitative measures prior to consideration of bicar- bonate. Diabetic ke toacidosis usually does not need bicarbonate unless pH is <7.0. Management of hyperkalaemia or tricyclic antide- pressant overdosage in the context of cardiac arrest. Sodium bicarbon ate helps reduce the sensation of dysp- neoa and restores plasma [H+] towards concentration s at which enzyme activity is usually most ef \201 cient. Sodium bicarbonate preparations Sodium bicarbonate can be given as an oral preparation; thi s is common for patients with chronic acidotic states such as chronic renal failure or rena l tubular acidosis. It is available as a 600mg tablet providing 7mmol Na and bicarbonate, or 500mg capsules providing 6mmol. Daily dosage depends on the degree of acidosis. IV solut ions are commonly available as the iso-osmolar \200\223 /l) or the 1.26% (150mmol Na+ and 150mmol HCO3 hyperosmolar 8.4% preparation (1000mmol Na+ and \200\223 /l or 1mmol/ml. The latter is corrosive to veins and HCO3 should be administered through a central line. Isoton ic bicarbonate is a convenient solution for restoring buffer base when hypovolaemia is sign i \201 cant. Sodium bicarbonate in dialysate \202 uids Bicarbonate-containing dialysate \202 uids ha ve now replaced acetate for intermittent dialysis. Acetate, together with lactate and citra te, are buffers which with a normal functioning liver are converted to bicarbonate. However , acetate dialysate proved to be problematic with respect to haemodynamic stability and bio compatibility. Lactate, hitherto the most common buffer for continuous dialysis systems, ha s been replaced by bicarbonate solutions. This is primarily because hyperlactataemia which is commonly observed with lactate dialysate confuses management even though there is effect ive buffering of acids. However, in those with hepatic dysfunction, it is not metabolized t o bicarbonate suf \201 ciently to be an effective buffer. Buffers are needed in dialysis f luid to deal with the 100mmol of \201 xed acid protons generated by metabolism each day b y normal adults. Kidney failure results in pro- gressive depletion of buffers because proto ns are instanta- neously buffered. Consequently, proton concentrations are extremely low an d are not effectively removed by dialysis. However, to avoid development of acidosis, buffe rs need repletion. Modern bicarbonate dialysate solutions contain between 30 and 40mmol/l, and not 25mmol/l as might be expected. This is in order that bicarbonate not only moves ef \201 ciently down a concentration gradient but also replen- ishes buffer de \201 cit. If lower concentrations were used, the plasma bicarbonate concentration 25mmol/l would be achi eved slowly. This would be a problem with the time Potential and theoretical dangers of sodium bicarbonate administration \200 Hypokalaemia through acid \200\223base changes and precipita- tion of dysrhythmias. Sodium load/hyperosmolar load. Overtreatment decreases ionized calcium, causing impaired myocardia l contractility and possible dysrhyth- mias and hypotension. Leftward shift oxygen dissocia tion and decreased tissue oxygen release. Intracellular acidosis due to dissolved CO2 movin g across the cellular membrane (relatively impermeable to bicarbonate anion) potentially im pairing myocardial con- tractility. The effect of bicarbonate administration on haemodynami c function has been debated vigorously. The evidence would suggest no detrimental effect on haemodynamics if given at a rate which does not rapidly change ionized calcium. Doses of 1 00mmol over 40 min appear to be clinically safe. Hypercarbia in ventilated patients if vent ilation is not temporarily increased during administration. \200 Quanti \201 cation of dosage Various formulations for correcting base de \201 cit have be en proposed. The bicarbonate concentration in extracellular \202 uid is twice that in int racellular \202 uid. Replacement in the \201 rst instance should match the extracellula r base de \201 cit. This is calcaulated on the basis that extracellular \202 uid is 20% body weight. 148 M PALAZZO limits imposed by intermittent dialysis or prove to be less effective with the slower \202 ow of continuous dialysis tech- niques. It is notable that dialysis often leaves patie nt very slightly alkalotic. It should also be noted that convection during haemo \201 ltra - tion removes buffer base; therefore, the replacement buffer solutions have to not only re place the corrected buffer removed but also provide additional buffer to replenish the orig inal buffer de \201 cit more rapidly. Cooper DJ, Walley KR, Wiggs BR, et al. Bicarbonate does not improve hemodynamics in critica lly ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann In tern Med 1990; 112: 492 \200\2238. Kaehny WD, Anderson RJ. Bicarbonate therapy of metabolic acido- sis. Crit Care Med 1994; 22: 1525 \200\2237. Kellum JA. Determinants of blood pH in health and disease. Crit Care 2000; 4: 6 \200\22314. Mathieu D, Neviere R, Billard V, et al. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical stu dy. Crit Care Med 1991; 19: 1352 \200\2236. Further reading Bersin RM, Chatterjee K, Arieff AI. Metabolic and hemodynamic consequences of sodium bicarbonate administration in patients with heart disease. Am J Med 1989; 87: 7 \200\22314. Stewart PA. Modern quantitative acid \200\223base chemistry. Can J Physiol Pharmacol 1983; 61: 1444 \200\22361. This page intentionally left blank 150 D THOMAS Blood Whole blood transfusion is rare, and usually blood compo- nents are given, targeted to the speci \201 c requirements of patients. The recognition of virally transmitted infection, t he apparent detrimental effect of transfusion of stored blood and supply problems have led to a far more objec- tive use of blood products. 1 Red blood cells are usually recommended when there is a percived need to correct hemoglobin/oxygen delivery. 2 Component use should be limited to correction of known de \201 ciencies as highlighted by either laboratory or near patient testing. patient testing results. As a general rule, a Hb level of 7 \200\2239g/ dl would be deemed adequate in all stable ICU patients. Patients with severe chronic cardiorespratory disease may bene \201 t from a haematocrit of between 28 and 33%, equiva- lent to a Hb of between 9 and 10g/dl. In younger patients without cardiorespiratory disease, a level of 70g/l would be suf \201 cient.